Research Corner

Research Corner

Recurrence Detection of Pediatric Germ Cell Tumors: A World Beyond CT

          April is testicular cancer awareness month! While there is some amazing work being done specifically in the field of testicular cancer, we decided to expand the umbrella a bit and look at a paper that focuses on pediatric germ cell tumors (while germ cell tumors are a subset of testicular tumors, they are also a subset of ovarian tumors). 

      How Multiple Myeloma Changed My Family                          Cancer is a word that surrounds us daily. We are constantly flooded with warnings that everything is potentially cancerous. News articles continuously tell us of a constant flood of daily products, foods, household appliances, and so much more that increase our risks of different types of cancer.  Studying biochemistry in college, I learned and studied cancer in great detail. Never did I imagine, however, that one day, it would be so intimately a part of my everyday life.               During the spring of 2014, as a Junior at Seattle Pacific University, I was lucky enough to travel to Peru to learn more about the dental field and work with Peruvian dentists to serve rural communities. It was my first big trip, and I was more excited than I had ever been in a long time. The trip itself was incredible. I experienced a completely different culture, and yet, the places I explored seemed at once very familiar to me, conjuring up memories of my hometown in Mexico. Although I loved the trip, I was excited to come home. I could not wait to share my experiences with my family. More than anything, I could not wait to hug them.      

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


     I remember coming home to the States hardly able to contain my joy to see my family, but instantly I realized something was different. I walked in and my mom’s friend was in the kitchen doing dishes, which seemed extremely odd; my mother would never let anyone do dishes or be in “her” kitchen. My mother was sitting on the couch, greeting me with the most beautiful smile, but I noticed she was also wearing a black back brace. Very odd.  I knelt in front of her and held her hands in mine. There was something really strange and deeply unsettling about seeing my mother sitting on the couch in her back brace, instead of walking around in her usual high heels. Despite what my brain was telling me, I managed to remain calm, hoping there was a reasonable explanation for the weirdness I was feeling.               My brother was in the living room, and he came over and hugged me. He told me in Spanish, “We have to be strong for Mom.” In that instant, I could no longer hold it together, and I started crying. We have all been in situations where we know we are about to receive bad news, and our minds immediately jump to the worst-case scenario. Most of the time, though, it never is as bad as it seems. My first thought was, “Mom has cancer.” At the same time, I was also hoping deep down, and had almost convinced myself, that whatever my brother was going to tell me was not as bad as cancer. My brother stuttered and said, “Mom has cancer.” In that moment, I could not do anything but sob uncontrollably. I felt the worst heartache I have ever experienced. My first thought was that my mom probably had breast cancer. I reasoned with myself, “It will be okay, based on what I know many women with breast cancer live for a very long time.” When I was finally able to choke some words out, I asked my brother what type of cancer she was diagnosed with. He told me she had “multiple myeloma.”  “Multiple what?!” I went back to hug my mom and just be with her in that moment. Although she was the one who had just been diagnosed with multiple myeloma, there she was holding me, loving me, and comforting me, like the incredibly strong and loving mother she is.               Today, I still remember that day as the worst day of my life. I went on to finish my Junior year of college. It was an extremely difficult year for me. I am very thankful, however, for my friends who made sure that I was okay at all times and kept me company. To this day, my closest friends continue to be one of my many sources of strength.      

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                 Immediately, my mother began her aggressive treatment to attack the myeloma, which included radiation therapy and intense chemotherapy. We began the dreaded weekly visits to the oncology center in Vancouver, WA.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                 The next couple of months after her diagnosis my mom and all of us were getting ready for the biggest day of our lives, her much anticipated bone marrow transplant. Luckily, she did not need a donor as her transplant was autologous, which means that her own stem cells would be cultivated and given right back to her. My mother is so strong; her own body saved herself and gave her another chance at life. After many rounds of chemotherapy, radiation, and physical therapy, as well as unexpected hospital visits, the big day had arrived:  March 27th, 2015.  The bone marrow transplant occurred at the Oregon Health & Science University oncology center in Portland, Oregon.  My sister had flown in from Mexico to be here with all of us. By now, it had been a whole year since her diagnosis, and I was now a senior in college getting ready to graduate.              College graduation finally arrived. I became the first person in my immediate and extended family to graduate from an American university. This was supposed to be one of the happiest days of my life, right? Although, I was extremely proud of myself, it was a bittersweet moment since my mother could not attend my graduation, as she was still recovering from her recent bone marrow transplant. My dad also could not be present as he was at home taking care of his beautiful wife. I knew that my parents were both cheering me on from Vancouver, WA, or as I like to call it “The ‘Couve”. My brother, his wife Adriana, and my uncle had traveled to Seattle to see me graduate. After the graduation ceremony I asked them to drive me to Vancouver so that I could be with my mother the same day of my college graduation. After the longest three hour car ride ever, I walked home with my cap and gown to share this moment with my parents. The recovery of her bone marrow transplant was very successful, but of course, came along with all side effects of a bone marrow transplant. The physical toll the transplant had taken on my mother did not shadow her inner strength and beauty. She is my biggest inspiration and daily I aspire to be like her.       

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                 Fast forward to this past spring 2018, and my family and I celebrated her third year of remission. My mother is one of the strongest women I have ever met. This past year has been even more exciting to see her physical strength slowly come back to her. This summer, she attended two weddings and left the house a little more for family dinners. She has even contemplated making a trip to Seattle with my dad to visit me, which is huge for her to say! I am currently working on my master’s degree and when I go home to visit, she will still make me tea to make sure that I am focused during my studies.      

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                 I admit that it has been an extremely difficult journey for my family and I, but there was something about this ugly and life-threatening disease that unexpectedly brought us closer together as a family. Throughout this entire process, my family and I have received so much support from other family and friends, and even hospital staff. The oncology nurses at the hospital are some of my favorite people to this day, and the doctors that I have met have been wonderful. Slowly they have become an extended part of our families. For some time, I have been wanting to return the favor and help other families who are in a similar situation as me. It is a challenging and dreaded journey, but the support makes it a bearable experience.               Joining the LiveSymile Foundation was something that happened unexpectedly and quickly. I am a big believer that when the right opportunity arises, you have to reach out and take it. The LiveSymile Foundation was one of those right and perfect opportunities for me.               I met Hakan Gem, the founder of LiveSymile, in the winter of 2018, while he was a fourth-year dental student at UW and I was working at a community health center where Hakan was assigned to do one of his clinical rotations. When the rotation ended, we friended each other on social media. A few months after, I noticed a personal post about Hakan’s mother and I was immediately touched by his extraordinary story. I also learned that he was starting a foundation to support cancer patients and their families. I wanted to learn how I could get involved and do something to represent and honor the journey my mother has been on. Hakan and I agreed to meet to go over a few of the logistics of a non-profit and how to get started. At that meeting, we both shared our stories about how cancer had influenced our families. I had to fight hard to hold back the tears when listening to his story and while sharing my own experiences. We both were on the same page; we wanted to create something beautiful to honor our mothers, in the midst of unthinkable pain.  Never did I imagine that I would walk away from that meeting with an offer to jump on board as one of the co-founders. I slept on it, thinking about the opportunity for several days. I wanted to ensure that I was the right fit to support and bring to life the visions and the values of the LiveSmyle Foundation. After mulling it over seriously, I accepted  to join LIveSmyle, and it has been the most exciting journey thus far. Hakan is a very motivated individual, and I am super excited to help bring his vision to life, while at the same time incorporating my own passion and infusing my own experience into LiveSmyle. I am beyond excited to be a part of such an amazing organization with Hakan, both of us inspired and driven to honor two amazing women who happen to be our mothers.

How Multiple Myeloma Changed My Family

            Cancer is a word that surrounds us daily. We are constantly flooded with warnings that everything is potentially cancerous. News articles continuously tell us of a constant flood of daily products, foods, household appliances, and so much more that increase our risks of different types of cancer.  Studying biochemistry in college, I learned and studied cancer in great detail. Never did I imagine, however, that one day, it would be so intimately a part of my everyday life.

      On Community Building in the Era of Division               It’s admittedly difficult to maintain an outlook of positivity if you keep up with today’s news cycle. From high profile court cases of sexual assault to the endless coverage of a narcissist president, we are inundated with news meant to provoke divisiveness and outrage.               Scroll through anyone’s Facebook feed and you can just feel the visceral disgust emanating off our screens. I’m tempted, as I’m sure you have been as well, to delete my social media accounts and turn away from this world of negativity and conflict.                But is that really the solution to this problem?               Perhaps it is. I have a number of friends who’ve happily deleted their accounts and pay little attention to the war of ideas being fought over the internet.               But perhaps it isn’t. Because doing so would close the door on one of the greatest opportunities we’ve created to build something special: online communities with the power to make positive and lasting impact on the world.               Right now, I want to press pause on the outrage machine that dominates our news feeds and tell you a story of how one such community is slowly coming together.                Back in July, as a beautiful summer was finally taking hold in Seattle, I received a Facebook message from an unlikely source.      

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                  The sender was Yarenni Mendoza, a colleague whom I’d met in dental school whose story shared many parallels with mine - a family stricken by cancer and a desire to do something about it.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                  Yarenni and I met after work one day, and it immediately became clear that a synergy was afoot. For the past few months, I had been establishing the legal foundation for a non-profit organization, and I was eager to find a partner who could help me develop it. Yarenni, on the other hand, was doing everything she could to support her family as they rode the turbulent rollercoaster of cancer care. But after having experienced the instability of that ride firsthand, she wanted to find a way to help make it smoother for others.                After sharing our stories with one another, it only made sense that we combine our efforts in the arena cancer awareness and support. And just like that, the core team of LiveSmyle grew from one to two.               But two people don’t exactly constitute a thriving community. So we got to work.               The first step was to establish a donor base who would support our vision of helping families undergoing cancer treatment. And my goodness, what a treat it was when over 15 family and friends agreed to become regular donors for the LiveSmyle Foundation.                The agreement was simple: each donor would pledge $1 for every social media engagement our Facebook page generated. And in three short months, this wonderfully generous group collectively raised over $6,500!               The next step was to find a meaningful recipient for these funds. And we did exactly that when we heard the Seattle Cancer Care Alliance needed help refurbishing components of their patient housing facility in South Lake Union.                In particular, patient beds had not been replaced in quite some time, so we  purchased and donated 4 complete bed sets to the housing facility. And with gracious acceptance from the team at SCCA, our community grew just a little bigger that day.     

  

    
       
      
         
          
             
                  
             
          

          
           
              From left to right: Yarenni Mendoza (LiveSmyle), Zara Crump (SCCA), Hakan Gem (LiveSmyle), Debbie Fraley (SCCA)  
           
          

         
      
       
    

  


                  And we’re not stopping there. We are hopeful that our next contribution will provide SCCA patients and their loved ones with fun experiences and positive memories as they visit Seattle for treatment. Two tickets to a Sounders FC match and two more tickets to the Cirque Du Soleil show “Volta” are to be raffled off in the coming days. We won’t know who will win them, but we will know that on the nights of October 8th and October 12th, four individuals whose worlds have been upended by cancer will find respite from their conditions, even if for just a couple hours.      



 
   
    
      

        

        
          
           
          

          
        

        

      

        

        
          
           
          

          
        

        

      
    
   

  
     
    
      
         
            
            
         
      
    
       
  

 






  
  
  

                  There is one more pillar in this emerging community that I haven’t yet mentioned. And that pillar is you, reading this right now. Ultimately, it’s the online engagement from people like you that fuels this entire operation. Not only do you help raise cancer awareness with each like, comment, and/or share, but you also help us raise the funds which our donors have agreed to pledge with each engagement.                And for that we want to say thank you. Moving forward, we will keep a running tally of those who remain the most engaged with our Facebook page and reward them with small gift cards to various cafes, restaurants, and retailers. Don’t expect too much! But it’s our way of showing how much we appreciate you helping us achieve our mission.                Make no mistake, I’m well aware that the LiveSmyle Foundation is but the smallest of fishes in a vast ocean of clickbait headlines and political/social dramas vying for your attention. Maybe it’s naive of me to think that we can leverage social media for something other than powering the outrage machine.               But if you see the same potential for positive impact that I see, and feel the same pull toward a world of compassion and inclusivity that I feel, then join us.               Join us simply by liking our page or by sharing our posts. Join us by telling your friends and family about us. Join us by becoming a donor. Join us if you feel like you can share your own skills and expertise with our team of two. Someday soon, I have no doubt that our team will inevitably grow to three. And then four. How big can this get? And who will those people be?               If you have been affected by cancer in any capacity, I offer you this opportunity to channel your loss, your anger, your frustration, your grief, whatever it may be, into a vehicle for good. If you fall into this camp, you have a community ready to accept you and implement your ideas for what constitutes a better life for cancer patients and their families.                Beyond the scope of cancer awareness, I want to leave you with my final and perhaps most important request. Aspire to use the tools at your disposal (the internet, social media, etc.) not to drum up controversy or maliciously spotlight those with whom you disagree. Rather, aspire to use these tools to build communities that will withstand this era of division. It may in fact be the most effective, if not only way we leave this era behind.     

  

    
       
      
         
          
             
                  
             
          

          
           
              The Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance in front of Mount Rainier. South Lake Union, Seattle, WA..

On Community Building in the Era of Division

             It’s admittedly difficult to maintain an outlook of positivity if you keep up with today’s news cycle. From high profile court cases of sexual assault to the endless coverage of a narcissist president, we are inundated with news meant to provoke divisiveness and outrage.

      A Bittersweet Time: The LiveSmyle Foundation               With graduation in the rear view mirror, I'm elated to have shared such a moment with my fantastic peers and all of our friends and families. I'm relieved that this long and difficult chapter is finally over. And I'm eager to tackle what lies ahead. But before embarking on the next journey, I have to take a moment and reflect on why this moment means so much to me.     


  

  


 
   
    
      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      
    
   

  
     
    
      
         
            
            
         
      
    
       
  

 


  

     
      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      
     

  





                  21 years ago, as a 5 year old boy, I watched my mom as she walked across the stage of the University of San Antonio School of Dentistry and earned her dental degree.     


  

  


 
   
    
      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      
    
   

  
     
    
      
         
            
            
         
      
    
       
  

 


  

     
      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      
     

  





                  That day only exists in my memory as a collection of a few, brief flashes, but I do remember feeling awestruck. I was definitely too young to understand what it all meant, but according to my grandmother whom I was sitting next to in the audience, I turned to her and said, "I'm going to be a dentist like her someday."               Of course I had no idea what I was talking about. I had no understanding of the countless hours of studying, preparation, and practice that it takes to become a dentist. And even now after having completed dental school, I still have no understanding of the added challenge that accompanies raising a young boy at the same time. Yet she believed she could do it, so she did. She was determined, independent, and fearless - qualities that I admired in her and appreciate more and more every day.               Words can't describe how deeply I miss her. At times, it's paralyzing to realize that I'll never see or speak to her again.  I wish so strongly that I could thank her for being the role model I try to emulate on a daily basis. But life often has little regard for our wishes, so what do we do? If I want to stay true to her character, there's only one thing I can do: channel the adversity of losing her as fuel to move forward and build a better world.               Today, LiveSmyle is having a graduation of its own. What was once a simple social media page is now the  LiveSmyle Foundation .                So what does that mean?                LiveSmyle will operate as it always has. I'll continue making weekly posts about important cancer news, facts, stats, historical figures, etc. But starting today, every time a post receives an engagement (like, comment, or share), a wonderfully generous group of donors will each put forth $1 in support of the foundation.                Where will the money go?                LiveSmyle is partnering with the Seattle Cancer Care Alliance to bring some light into the lives of cancer patients. Many patients of the SCCA fly from all over the region to receive their treatment here, and for many of those folks, Seattle will only be the place where they got chemo, radiation, and/or surgery.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                  The LiveSmyle Foundation is going to change that. Donations will be used to purchase tickets to events and experiences around Seattle at the request of patients and their families. Whether it's visiting popular tourist sites, attending sporting events, visiting a museum, enjoying a nice dinner at a local restaurant, or anything that we can make happen, patients of the SCCA will be given the opportunity to enjoy Seattle before, during, or after their treatments.               Let's use social media to do something good. Every like, comment, and share of LiveSmyle's content will not only raise cancer awareness, but it will also raise funds to help patients and their families through tough times.  With your help, we'll make it happen!

A Bittersweet Time: The LiveSmyle Foundation

With graduation in the rear view mirror, I'm elated to have shared this moment with my fantastic peers and all of our friends and families. I'm relieved that this long and difficult chapter is finally over. And I'm eager to tackle what lies ahead. But before embarking on the next journey, I have to take a moment and reflect on why this moment means so much to me.

      Why the War on Cancer is Wrong               "She battled cancer for about three and a half years and lost her fight in June, 2015." When I first heard myself say these words in response to how long my mother had been "fighting" cancer, it just didn't feel right. But throughout the entire process, from diagnosis to death, this was the metaphor surrounding her illness. Our friends, family, doctors, and researchers -  literally everyone  was engaged in a battle for the ages. But how did we come to think of cancer in this way? And is it possible that it's actually doing more harm than good?  1943, the War Begins               On the heals of World War II, the war on cancer escalated quickly and quietly. A self-made, powerful businesswoman by the name Mary Woodard Lasker was a rising socialite in the bustling scene of New York City. Prior to the 40s, Lasker had been a wildly successful saleswoman and entrepreneur who would eventually be described as having "legendary social and political energy."     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                  Following the death of her mother who had brushes with both cancer and heart disease, Lasker redirected her professional efforts from the business world to public health activism. Her first step was to get a pulse on the landscape of cancer research, so she visited the American Cancer Society (then called the American Society for the Control of Cancer) in 1943, and what she found was disappointing.               "The visit left her cold. The society, a professional organization of doctors and scientists, was self-contained and moribund, an ossifying Manhattan social club. Of its small annual budget of about $250,000, it spent an even smaller smattering on research programs (Emperor of All Maladies)."                So Lasker got to work, upending the entire system in her signature way.               In four short years, she and her team transformed the fledging society by replacing the leadership, rewriting the bylaws and constitution, and fundraising an incredible twelve million dollars - a near 5000% boost to their budget.               How did she do it?               By deploying one of the most powerful metaphors that we have at our disposal: war. She shaped the public's perception of cancer from a disease that people were too frightened to talk about, to an enemy that needed ruthless and systematic eradication. She not only rallied doctors and scientists, but also celebrities and philanthropists. She took to the radio waves and magazines and newspapers to raise awareness around this silent and devious enemy. This was a war she couldn't fight alone, and her previous experience as a businesswoman gave her all the skills she needed to rally everyone to her cause.               Most people would agree that we are an innately tribalistic species, and if we detect a threat to our people, we have an extraordinary capacity to collectively neutralize that threat. And herein lies the troublesome double-edged sword of "fighting" cancer. There's no doubting the immensely positive impact that Lasker had on cancer awareness, advocacy, and research by appealing to this side of humanity. Her efforts would culminate in the signing of the 1971 National Cancer Act, which would pledge more money and resources toward cancer research and treatment than ever before. And the progress that we have made as a result is unbelievable.     


  

  


 
   
    
      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      

        
          
             
              
                    
              

              
                
              
                
             
          
          
        

        

        

      
    
   

  
     
    
      
         
            
            
         
      
    
       
  

 


  

     
      

        
           
        

        

      

        
           
        

        

      

        
           
        

        

      
     

  





                  But what was the tradeoff that we made when we decided to go to war? And how can we detect when the impact of this mentality is no longer beneficial?                By listening to the "soldiers" we send into battle.  The Price for Glory               Everybody loves an underdog who wins. Whether it's David toppling Goliath, or the proverbial Cinderella team dancing their way through the March Madness tournament. You see where I'm going with this - we all want to view our friends and family who are diagnosed with cancer in the same light. We want them to embody the spirit of a warrior who will fight against and beat all odds. I know, because this is how I wanted to view my mother as she went through treatment.                But it was a mistake and in hindsight, I wish I hadn't. Because the reality that we must face is that we're not all warriors.  And having cancer is not a battle that we should force people to fight.                Why?               Because "fighting" cancer shifts the burden of victory, or worse, the guilt of loss, squarely on the shoulders of the patient. Consider what is implicated when the cancer is out of control and can no longer be treated.  Would it have been possible to win if only the patient fought harder?  And while at first the metaphor may be inspiring, it falls apart in the throes of chemotherapy, radiation, and surgery.               Today's standard for cancer therapy is a much crueler world than many of us want to acknowledge. Sure, we all have an abstract sense of its physical challenges - the nausea, the hair loss, the energy drain, etc. But what most of us lack is a fundamental understanding of how it erodes our psyche - the isolation, the depression, the bitter confrontation with one's own mortality.                In the midst of this physical and mental trial, our loved ones are urged to remain strong, to never give up, to keep fighting. Making these suggestions is a blatant, and often completely unintentional disregard for the enormity of the existential task that is surviving cancer.                So does this mean we should preach the opposite message? To give up immediately in the face of a terminal diagnosis?                Absolutely not.  A New Framework               What I am advocating for is a collective shift in how we talk about cancer. If we move past this metaphorical war and begin to understand how cancer actually impacts the human condition, not only will we be more successful in how we support our loved ones as they go through treatment, but we will be more successful in how we treat cancer itself.                Let me explain.               When we replace words like "battle" and "fight" with "diagnosis" and "treatment," we paint a more realistic picture of the disease. And it creates a more approachable environment for those having to deal with it. So rather than asking, "how long have you been battling cancer?" a better question might be, "how long ago were you diagnosed?" And if you want to show your support to a friend or a loved one, saying "I'm here for you through your treatment," might be a better option than "keep on fighting, I know you can win." Take a look at cancer survivor and writer  Xeni Jardin's opinion  on this.               Changing our rhetoric also forces us to understand cancer in its truest form. What does it mean to be diagnosed? For starters, cancer is the term we use to describes a set of diseases that share the common characteristic of abnormal cellular growth. Diagnosis is confirmed under a microscope when cells exhibit very distinct patterns that suggest cancerous transformation. So why do the current treatments have such devastating side effects? Cancer cells grow rapidly and have the potential to spread and invade to other parts of the body. Our classical chemotherapeutics target all rapidly dividing cells including those found in your hair follicles and digestive tract, hence the dramatic hair loss and nausea.               From here, we can ask more nuanced questions: how does the next generation of therapy promise better efficacy with fewer side effects? Right now, there is a colossal effort in the research community to find out exactly how cancer cells differ from healthy cells  at the molecular level . Given that there are probably more molecules in a single cell than there are stars in the Milky Way galaxy, you can appreciate the grand scale of this challenge. But with technological advancements in areas such as immunology, big data, and even machine learning, the problem is slowly being solved. And your ability to recognize which efforts are the most promising is a direct function of your understanding of cancer. Which is why you shouldn't resort to metaphorical thinking, but stick to more accurate descriptors that force you to comprehend what this disease really is. This gives you the added benefit of knowing how to best prevent cancer in your own body.        </iframe>" data-provider-name="YouTube"                      Today marks the beginning of a new year and an opportunity for all of us to start something new. Let 2018 be the year you transform your thinking about cancer. Challenge yourself to use more accurate, non-metaphorical words when referring to this disease. And with this new framework, let us enhance our support and progress toward a world free of cancer.  Further Reading    Illness as Metaphor - Susan Sontag    Emperor of All Maladies - Siddhartha Mukherjee

Why the War on Cancer is Wrong

             "She battled cancer for about three and a half years and lost her fight in June, 2015." When I first heard myself say these words in response to how long my mother had been "fighting" cancer, it just didn't feel right. But throughout the entire process, from diagnosis to death, this was the metaphor surrounding her illness. Our friends, family, doctors, and researchers - literally everyone was engaged in a battle for the ages. But how did we come to think of cancer in this way? And is it possible that it's actually doing more harm than good?

      How Billions are Wasted on Cancer Drugs                As an aspiring healthcare provider, this is perhaps the hardest pill to swallow (no pun intended). Our capitalist economy has unquestionably contributed to the immense rate of technological and scientific progress over the years. Everywhere you turn a new device, innovation, or application is springing up to make our lives easier. But is this the correct method to solve the indisputable healthcare crisis that has enveloped the United States? Or more importantly, is it moral to profit from those who are suffering from sickness? It's a simple question that reveals the complexity underlying the US biotech industry.  Drug Companies Are Businesses                It's been shown over and over again - America has the highest healthcare costs per capita and the some of the poorest health outcomes in the developed world. And the rising cost of pharmaceuticals only exacerbates this problem for many families.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                   Take Lauren Baumann, a single mother who relies on the drug Gleevec to manage her chronic myeloid leukemia -  a type blood cancer. Her co-pay (the amount of money she pays after insurance kicks in) is $2,200 per month. Even with a full-time job, she has been forced into bankruptcy in order to pay for her medication. Once upon a time, this drug only cost a third of what it costs today. How did this happen?        </iframe>" data-provider-name="YouTube"                       Gleevec is manufactured by the pharmaceutical giant Novartis which rakes in $5 billion a year from this drug. In 2001, Gleevec cost $2,600 a month for patients. Now, it's around $9,200 per month. The company justifies this increase by stating that the money is going toward the research and development of new drugs. A noble effort for sure, but one that's difficult to fully believe given the  $12 million compensation of Novartis CEO Joseph Jimenez in 2015 alone .                Let's look into one fascinating reason why cancer drug prices are skyrocketing.  It's All About Serving Size                 Herceptin  is an effective targeted therapy developed by Genentech and administered via blood infusion at hospitals for the treatment of breast cancer, the leading cause of female cancer mortality. Prior to 2017, the drug would come in a 440 milligram shareable vial which could be distributed between multiple patients as needed.                In May of this year, Genentech announced that it would be discontinuing the larger, shareable vial for a smaller,150 milligram single-use vial. It may not be obvious right away, but this change resulted in a huge money drain for patients and an equally large profit margin for Genentech.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                   The amount of Herceptin a patient needs is determined by their bodyweight. One hospital administrator in California calculated that the average patient needed about 340 milligrams per infusion based on their bodyweight. But since the vials are single-use and come in 150 milligram increments, the average patient would need 3 vials (450 milligrams total) and waste approximately 110 milligrams per infusion. At $9 per milligram, that's roughly $1,000 wasted per infusion! And each patient needs multiple infusions every week for up 64 weeks. The amount of money wasted here is sickening. And the unused drugs remaining in the vials can't be reused, so they're discarded. But the patient gets billed all the same as if they used every drop.                 And it's not just cancer drugs that are wasted in droves , even the way that generic eyedrops are packaged make us use more than we need.                Once again, justification was provided by Genentech for their use of smaller vials. The change in vial size would help their worldwide supply chain become more reliable and thus distribute the life-saving medication more easily. Even if that were true, Genentech is grossly overlooking the financial burden they are placing on these patients and enjoying greater profits as a result. You would think that regulatory agencies like the FDA might have something to say about this. But they are tasked with the safety and efficacy of these drugs, not the cost or method of distribution. So this behavior continues unchecked.   The Solution Is Simple, Changing Your Philosophy Is Not                Studies have demonstrated how wasteful these single-use vials are among other senseless practices of pharmaceutical companies.  A 2016 publication by Dr. Peter B. Bach , a physician at the Memorial Sloan-Setting Cancer Center, concluded that 10% of the top 20 cancer drugs were thrown to waste in 2016. How much did those wasted drugs cost for patients and their insurance companies?                 $1.8 billion.                 Yes, with a B. In a single year.        </iframe>" data-provider-name="YouTube"                       Reverting back to shareable vials would almost immediately fix this problem. So why haven't we done it? Because the philosophy driving these giant pharmaceutical corporations prevents them from doing so. Those $1.8 billion aren't wasted for Genetech, Novartis, and the like. For them, this is a huge positive. They are selling more drugs and making more money, which is excellent news for their executives and shareholders.                And herein lies the crux of the entire issue.                Who should the companies that operate in the field of healthcare be accountable to? Their CEO's and top ranking officers? Their shareholders? Or the people who need their product to stay alive?                In today's world, our insurance companies, pharmaceutical companies, and many treatment centers hold their bottom lines on a higher a pedestal than their patients. Of course, without money these organizations couldn't provide healthcare. But at some point a line must be drawn to prevent the entire field of healthcare from slipping into a landscape that is dominated by capitalist forces.  A 2004 publication by a Bay Area news organization  reported that the top 5 paid executives at Genentech were compensated a total of around $63 million. The line, in my humble opinion, was crossed long ago.                A company decides it needs to improve the efficiency of its supply chain, but as result, throws thousands of patients into insurmountable economic distress. This simply is not fair. This simply is not just. Healthcare giants must transform their philosophies to protect these vulnerable populations. It's not a question of profit versus loss, it's a question of right versus wrong.         </iframe>" data-provider-name="YouTube"

How Billions are Wasted on Cancer Drugs

              As an aspiring healthcare provider, this is perhaps the hardest pill to swallow (no pun intended). Our capitalist economy has unquestionably contributed to the immense rate of technological and scientific progress over the years. Everywhere you turn a new device, innovation, or application is springing up to make our lives easier. But is this the correct method to solve the indisputable healthcare crisis that has enveloped the United States? Or more importantly, is it moral to profit from those who are suffering from sickness? It's a simple question that reveals the complexity underlying the US biotech industry.

      What It was like to Work in a Cancer Lab                Over the last three months, I had the incredible opportunity to work full time at The Fred Hutchinson Cancer Research Center in Seattle. Opened in 1975, the Hutch is part of a network of NCI-designated cancer centers around the country. In it's brief 42 year history, our center has produced three Nobel laureates, a consortium with UW Medicine and Seattle Children's called The Seattle Cancer Alliance, and countless biomedical discoveries and innovations. This is my account as a fledging dental student/scientist of what it was like to peek behind the grand curtain of cancer research right here in my home town.                 The monumental scale of their effort is immediately apparent when you step on the 15-acre, 13-building, 1.5 million square foot campus located on the south end of Lake Union. The red brick exterior gives a sense of timeless tradition which contrasts nicely with the pristine corridors decorated by scientific posters and awards. There's a sense that important work is being done here, and as an outsider looking in on day one, I'd be lying if I said I didn't feel a bit intimidated.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                   But that feeling quickly subsided as I met my fellow co-workers in the lab. Friendly, passionate, and exceedingly intelligent, they welcomed me in despite the growing size of their team. Our leader, a head and neck cancer surgeon at UW and principal investigator (PI) at the Hutch, employs a team of 2 post-doctoral fellows, 2 ENT residents, a lab technician, and for a brief period of time, a dental student eager to get started in the field of cancer research.                The focus of his research lab is head and neck cancer. In particular, the team concentrates on the most common form of head and neck cancer known as squamous cell carcinoma (SCC). These cancers typically arise in the tissues that line the inside of the mouth, nose, and/or throat.                 A great majority of SCCs carry a mutation in a gene called TP53 which encodes for a crucial tumor suppressor protein. As it turns out, TP53 mutated SCCs are especially vulnerable to a targeted therapy called AZD1775 - a protein (WEE-1) kinase inhibitor. It essentially operates by blocking the action of a key enzyme that the cancer cell relies on. In combination, the TP53 mutation and targeted therapy render the cell too unstable to survive. Our PI discovered this cancer cell vulnerability back in 2014, and he is currently completing a promising phase I clinical trial using that drug.                My role over the summer was to assist a post-doctoral fellow in the lab as his focus was on human papilloma virus (HPV) related SCC. It's becoming more and more apparent that a rise in HPV infections is leading to a rise in oral cancer rates, so research in this field is really beginning to pick up.                The virus induces cancer by inserting its own genes into the human genome. E6 and E7 are two specific oncogenes that these viruses insert into their host DNA. From there, the host's own DNA replication mechanism transcribes the E6 and E7 oncogenes producing oncoproteins. These oncoproteins go on to inactivate key tumor suppressor genes like TP53 and RB, effectively removing any braking mechanism the human cell may use to slow it's own growth. From the virus's standpoint, this is hugely beneficial. The more the host cell replicates, the more it gets to replicate. From our standpoint, this can obviously lead to devastating outcomes such as cancer, which is why it's so crucial that we develop a deeper understanding of how viral infections impact our biology.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                   Transitioning from the clinic to the lab was certainly a change of pace. In the clinic you get a sense that you're always battling the clock. Between waiting for faculty approval, constantly checking patient comfort, or collecting all your supplies and instruments for the procedure, you feel lucky on days that you get a full hour for lunch. It can feel like chaos at times, which is not necessarily what you want to hear from the person wielding sharp objects around your face.                But in the lab, the setting is much calmer. People tend to set their own hours and work when they want to. I saw my workday slowly shift from the usual 7:30AM - 4:00PM routine to a 9:30AM - 6PM routine.                Workflow in a lab setting is also very different from the clinic. First off, the person-to-person interaction is no longer there, and I have to admit it's something that I missed far more than I anticipated. The main subject of your labor no longer requires communication, because the main subject of your labor is now a Petri dish or a test tube. The energy and pace of clinic was definitely an absence that I felt.                 But there is a certain zen-like focus that this setting lends itself well to. I must admit that I enjoyed the sense of seclusion and independence that I didn't necessarily have in the clinic. In the lab, you can throw in your earbuds and work away in the cell culture room without having to report to anyone - and that can be pretty nice on days when you're feeling antisocial.                Overall, the experience opened my eyes to the rigor that the scientific process demands. Every single experiment or reaction is repeated at least 3 times, often more, to confirm the validity of any one result. Sometimes you spend an entire day setting up a reaction only to have it fail because you accidentally skipped step 2 earlier that morning. Sometimes you do everything absolutely right and get results that make no sense, because well, that's science.                But there are those rare moments when you look over your data for the first time and discover something interesting. Maybe it answers the question that you've been addressing all along, maybe it raises a new one. That's the most exciting part about being a scientist. You are literally standing on the frontier of human knowledge and peering into the vast unknown. If you're lucky, you find yourself in the unique position to advance that frontier even if it's just by a baby step. Over time, those baby steps culminate into what we see today: an explosion of information about the universe around us, and most importantly, about ourselves. What's incredible is how we can use that information to improve the quality of human life. But even without that, the act of discovery is just plain cool.                  As the great scientist Carl Sagan once said, "We are a way for the cosmos to know itself."

What It was like to Work in a Cancer Lab

              Over the last three months, I had the incredible opportunity to work full time at The Fred Hutchinson Cancer Research Center in Seattle. Opened in 1975, the Hutch is part of a network of NCI-designated cancer centers around the country. In it's brief 42 year history, our center has produced three Nobel laureates, a consortium with UW Medicine and Seattle Children's called The Seattle Cancer Alliance, and countless biomedical discoveries and innovations. This is my account as a fledging dental student/scientist of what it was like to peek behind the grand curtain of cancer research right here in my home town.

      A Deep Dive into Targeted Therapy                  If you take a cursory glance at the headlines regarding cancer research today, you'll see the word  immunotherapy  an inordinate number of times. It's the hottest story in cancer research right now. But is it the only one? The answer is no. There's another field that holds just as much promise and is being developed just as rigorously, but its impact is overshadowed by the hype surrounding immunotherapy. This month, we'll set aside the hype and focus our light on the fascinating landscape of targeted therapy - an equally capable and yet often overlooked field of cutting edge cancer research.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


     A Moving Target                  What exactly is the target in targeted therapy? Put simply, the target refers to critical molecules or enzymes that cancer cells rely on to survive. The idea behind targeted therapy is relatively simple to grasp: if we can eliminate the critical molecules that cancer relies on, we can eliminate cancer itself. But like many things in biology and in life, this is much easier said than done.                  Technically, targeted therapy is a form chemotherapy, which is a systemic treatment for cancer using oral or IV medication. But it's different than what most people think when they think of conventional chemotherapy. We often associate chemo with its unmistakable side effects: severe nausea, repetitive vomiting, generalized hair loss, etc. But this actually refers to a class of chemo known as cytotoxic chemotherapy. In general, these drugs kill rapidly growing cells in a non-specific way. Great, since the very definition of cancer is uncontrolled cell growth. But not so great when these drugs kill rapidly growing cells that are non-cancerous - like the ones lining your bone marrow, GI-tract, and hair follicles.                   Conventional chemotherapy has been around since the mid-1950s, and while we've seen refinements to cytotoxic drugs, their side effects and lasting damage to the body leave much to be desired. Targeted therapy seeks to eliminate these side effects. We want to move away from damaging healthy cells and hone our therapeutic strikes on cancer cells exclusively. To do this, we need to understand how cancer cells are different from healthy cells on a whole new level. The molecular level to be precise. And the arena in which these differences are most apparent is in the cell cycle. Let's have ourselves a little look.        </iframe>" data-provider-name="YouTube"         The Cell Cycle Explained                  To understand how most chemotherapies work, you need to understand the cell cycle. This is the natural life cycle of our cells, and it results in DNA replication and cell division.        </iframe>" data-provider-name="YouTube"                         The cycle is broken into four major phases: G1 phase, S phase, G2 phase, and Mitosis (that annoying thing you had to memorize back in AP Bio). Let's break it down.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                    G1 Phase  - This is the initial growth phase of a cell that has committed itself to replication and division. During G1, metabolic activity within the cell surges. The protein supply chain ramps up by increasing DNA transcription (conversion of DNA to RNA) and translation (conversion of RNA to proteins). These proteins contribute to increase in metabolic activity. Cell organelles like the mitochondria and ribosomes are duplicated over and over so that there are enough for two independent cells. And most obviously, the cell significantly grows in size to accommodate for these extra components.                 S phase  - This is the phase during which the entire DNA is replicated within the cell. Protein and organelle manufacturing slows down so that the blueprint (i.e. the DNA) can be copied with high fidelity. Remember biology 101: copying errors in DNA replication are mutations, and while most mutations can go unnoticed, the most severe ones can lead to horrible diseases, like cancer. So needless to say, this phase is pretty important and the cell knows it.                 G2 Phase  - This is the second growth phase of the cell, and it immediately precedes cell division. As such, much of this phase is dedicated to preparing for division by another round protein manufacturing, spindle formation, and DNA quality control. Once the cell is prepped and it's ready for division, we move into Mitosis.                 Mitosis  - This is final step of the cell cycle where division actually takes place. It also happens to be the one that most biology students are very familiar with. Remember the sub-divisions of Mitosis? Prophase, Metaphase, Anaphase, Telophase? My college professor had a great acronym to help us remember these sub-divisions: PMAT or Pour Me Another Tequila.   #nerdjokes.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                     Okay so now that we're experts in the cell cycle, how do we relate it back to cancer? Well, in between some of these phases are critical checkpoints that are vital to healthy cell division. In particular, the G1/S checkpoint and the G2/M checkpoint are the most significant.                 G1/S Checkpoint  - Before proceeding to S phase for DNA replication, the cell needs to ensure that it is truly ready for the task. If there's insufficient growth during G1, the cell enters a quiescent stage known as G0 and replication is put off for another time. The G1/S checkpoint is also significant because once it's passed, the cell is irreversibly committed to division or death.                 G2/M Checkpoint  - This is the final check before the cell enters mitosis and actually divides. A critically important step in the G2/M checkpoint is the proofreading of replicated DNA to ensure no major errors or mutations have occurred. If the cell detects any irregularity in the DNA, it will steer away from mitosis and begin the process of apoptosis, otherwise known as programmed cell death. It's a built in protection to prevent abhorrent cells from dividing - a defensive harakiri, if you will.        </iframe>" data-provider-name="YouTube"                         If these checkpoints are not obeyed and the cell flies through them during the cycle, cancer is a very likely and common outcome. The only reason that cells actually stop for these checkpoints is because specific regulatory molecules force them to. Once such molecule, probably the most studied in the history of cancer research, is the one and only p53.                   p53 is a central figure throughout the cell cycle. Its responsibilities include stopping cells at their appropriate checkpoints, activating DNA repair pathways if it detects damage, initiating apoptosis if necessary, and much more. It's rightly been referred by many as the guardian of the genome.                  In so many cancers, we find that the genes encoding p53 have been mutated. For example, we know that around 62% of head and neck cancers harbor a mutation in p53. That's a huge percentage! It speaks to the importance of this molecule as a tumor suppressor.                   So how can we leverage our knowledge of these mutations to develop targeted therapies? It begins by understanding that cancer cells behave in predictable ways. We just have to know where to look.  Hello Cancer, This is an Intervention                  Imagine you're a cancer cell. You have a p53 mutation, so as you speed through the cell cycle, you don't care about stopping for checkpoints. While this may serve to your advantage at first, it invariably leads to your own destruction.                   Why?                  Because even cancer cells need to stop and make sure their internal processes are running correctly. If you keep blowing past the checkpoints and accumulate more mutations in other vital genes, you won't survive through many more cycles. So what do you do? You rely more heavily on other molecules similar to p53 to protect your mutated version of DNA. You do this by upregulating - i.e. producing more - molecules such as pRb, WEE1, or VEGF to name a few.                   And herein lies the beauty of targeted therapy. We can target these molecules that cancer cells rely on to survive, and we can do this with such precision that we spare healthy cells in the process. So in an ideal world, targeted therapy promises to eliminate cancer by exposing and exploiting its unique dependencies.   To Infinity and Beyond                  To be clear once again, this is much easier said than done. Each tumor has its own genomic profile and therefore its own pattern of molecular expression. Even cells found within the same tumor have different mutations and proteins driving their growth. So even if you're able to target one tumor successfully, that doesn't guarantee that you'll be able to target the next one in the same way.                  So where does this leave us?                  Right now, thousands upon thousands of genes, proteins, and drugs are being investigated for their respective roles in the cell cycle. And this research is being translated into tangible results. The FDA approved the first targeted therapy, tamoxifen, for HER2+ breast cancer back in 1977. Since then, our understanding of cancer genome profiles, tumor biomarkers, and molecular expression has evolved to the point that we now have hundreds of targeted therapies on the market. And there are literally thousands of clinical trials going on right now to advance the efficacy of these targeted drugs.                   This is great news, obviously, but it raises a concern in my mind. Given the complexity of the cell cycle and the sheer number of potential targets, we are generating an overwhelming library of data and information. So much so that even the best clinicians are hard pressed to keep up with the latest developments. Paradoxically, this means that cancer patients who would be great candidates for new drugs may miss out because there are simply too many options for doctors to keep track.     

  

    
       
      
         
          
             
                  
             
          

          

         
      
       
    

  


                     Because of this problem, I predict that a couple of novel solutions will rise. I believe medicine will soon deploy machine learning and artificial intelligence to connect patients to appropriate therapies. Imagine feeding a biopsy sample to an "intelligent" diagnostic device that can detect the entire mutational landscape of the specimen. From there, the unique set of proteins and molecules that the cancer relies on would be identified, and an algorithm could work out which drug or drug combinations would be most efficacious for that patient.                   Of course, this still doesn't solve the problem of the genetic and proteomic heterogeneity that we observe even within the same tumors. In other words, a biopsy from one area of the tumor may spit out different results from a biopsy taken from another area of the tumor. To solve this, we'd truly need a revolutionary solution.                  I can imagine a day that this is solved by synthetic nanorobotics. Swarms of tiny, intelligent machinery floating through our circulatory system would constantly survey our body for cancer. If one detects an abnormality, it reports the finding to the cloud and generates a report for the best course of action. These nanobots could even be loaded with the drug of choice and deposit it in exactly the right place. Heck, we may not even needs drugs at that point - the bots may be able to fix or eliminate the cancer cells themselves.        </iframe>" data-provider-name="YouTube"                         While it is fun to envision such a future, these examples still remain under the purview of science fiction. But perhaps not for long. In any case, one thing remains clear: medical scientists must continue to generate this data if we ever hope to make that future a reality. A reality that is free of cancer. That's the one I want to live in.   

A Deep Dive into Targeted Therapy

              If you take a cursory glance at the headlines regarding cancer research today, you'll see the word immunotherapy an inordinate number of times. It's the hottest story in cancer research right now. But is it the only one? The answer is no. There's another field that holds just as much promise and is being developed just as rigorously, but its impact is overshadowed by the hype surrounding immunotherapy. This month, we'll set aside the hype and focus our light on the fascinating landscape of targeted therapy - an equally capable and yet often overlooked field of cutting edge cancer research.