How Is Cancer Research Doing These Days?

              Welcome to the first post in the Cancer News Blog! I don’t know how you did it, but you’ve managed to find this nerdy corner of the internet, and believe me – it’s about to get nerdy. This blog will be updated on the first Monday of every month. In this month’s post, we’ll cover a couple important topics in the realm of current day cancer research. The first topic addresses how some media outlets may have overstated a recent scientific discovery. And the second topic covers two emerging fields of cancer therapy that show great promise for the future of cancer treatment: targeted therapy and immunotherapy.

Cancer Research in the Media

Are 66% of cancer cases really just due to bad luck?

              A study published in the journal Science about two weeks ago received a great deal of attention when major news sources started claiming “Most Cancer Cases Arise from ‘Bad Luck’” or “DNA ‘Typos’ May Cause 66% of Cancer Mutations.” They pointed to a study led by two prominent cancer researchers, Cristian Tomasetti and Bert Vogelstein, that seemed to make a controversial statement about our chances of developing cancer. Supposedly, two-thirds of cancer cases are simply due to bad luck and there’s nothing you can do about it. Don’t feel too discouraged though, because this interpretation is perhaps incomplete.

              In reality, the study describes a relationship between cancer incidence and cell division using statistical analysis. Put simply, as the number cell divisions increases over one’s lifetime, so does their risk of developing cancer. Now this seems like an obvious fact that we’ve known for a while, but this study digs a little deeper and finds something interesting.

              As our cells replicate DNA, they inevitably make mistakes which we call mutations, and the accumulation of very specific mutations is what ultimately leads to cancer. Interestingly, most mutations occur in sections of our DNA that are irrelevant to cancer. So even though a single cell may generate tens of mutations every time it divides, just about all of those mutations are inconsequential. But, sometimes these mutations occur in areas that are critical to the development of cancer, like oncogenes or tumor suppression genes, and that’s where the “bad luck” comes in.

              Using a statistical model, these researchers discovered that 66% of the mutations that are found in cancer cells are attributed to replication errors that occur in segments of DNA relevant to cancer. Many have interpreted this finding to say that developing cancer is simply a matter of bad luck, but again, this line of thinking doesn’t give the full picture. Normal cells must typically accumulate more than one mutation before they transform into true cancer cells. Thus, lifestyle factors like smoking, obesity, or UV exposure can still play a huge role in preventing or promoting cancer, and we have the power to decide how we engage in those activities.

              Nonetheless, the authors of this study make an important point when it comes to understanding cancer risk. The current paradigm mainly focuses on environmental and hereditary factors when assessing one’s risk of cancer, and this can pack a tremendous amount of personal responsibility or guilt behind a cancer diagnosis. People end up asking: I did everything right – I eat healthy, I never smoke – why did I still get cancer, what did I do wrong? This study provides one possible answer to that question by adding a third major component in assessing risk: DNA replication errors.

              It’s a delicate balance between limiting harmful exposures to mitigate risk and accepting the fact that cancer is sometimes an inevitability of our complex biology. Understanding that replication errors are indeed non-preventable may help alleviate some of that personal burden that comes with diagnosis. Awareness of this fact is the first step in driving more research to uncover the mechanisms that underlie cancer biology, and it will perhaps lead us down a path where we can reverse these unfortunate inevitabilities.

The Future of Cancer Therapy   

What treatments are the focus of today’s research?

              Current cancer research is centered around a couple key questions when it comes delivering treatment.

              1)   How can we increase the effectiveness of the medicine we give to cancer               patients?

              2)   How can we minimize the intense side effects of traditional                                           chemotherapies?

              The answers to these questions may lie in two emerging fields of cancer research: targeted therapy and immunotherapy.

              Targeted therapy has emerged as a consequence of the vast amount of data and information that has been generated by basic scientific research on how a cancer cell functions. For example, we know that all cancers arise from mutations in our DNA. But why is that? What actually happens to the rest of the cell when DNA is mutated in the wrong way? You can think of DNA as the instruction manual that a cell uses to make the tools it needs for normal function. These tools are things like proteins, enzymes, or other molecules like RNA that all play critical roles in healthy cells. When the instruction manual has an error in the form of a mutation, some of these tools are no longer made, or they are made incorrectly. As you can imagine, when a cell does not have the right tools to regulate its own growth, cancer is often the consequence. But whereas traditional chemotherapies generally act on all cells that replicate quickly, cancerous or not, targeted therapy hones in on the defective tool that has led to cancer. We can do this by sequencing the DNA of cancer and finding exactly where the instruction manual has incorporated a typo. From there, we find out which tool is no longer functioning properly, and we can develop a targeted strategy to eliminate the cancer.

              For example, it was reported last month that researchers at Mount Sinai Hospital and School of Medicine in New York City have been focusing on a specific mutation found in some breast cancers. This mutation results in a shift in the metabolism of cancer cells that ultimately becomes critical for their energy production, and the researchers identified the main enzyme that the entire new metabolic process relies on. You can think of this enzyme as a knife that the cancer cell uses to cut its food into digestible pieces, and without it, the cell can’t survive. Naturally, the researchers targeted this important tool and inactivated it thereby starving the cancer cell. Their idea has worked in mouse models, and they are now looking to start phase I clinical trials with humans.

              Immunotherapy is another fascinating field in cancer research that has recently been exploding with growth. This type of cancer treatment, which was actually first introduced in the late 1980s, leverages the sophistication of our own immune systems to eliminate cancer. Merkel cell carcinoma is a rare but deadly form of skin cancer that has the extraordinary ability to inactivate the body’s immune system. Normally, our body has immune cells that can run surveillance and destroy emerging cancer cells as they develop. But some cancers are able to avoid our natural search-and-destroy system by using a specific protein on the surface of their cell membranes. Think of this protein as a key. When a cancer-fighting immune cell approaches a cancer cell, the cancer cell uses this key to inactivate the immune cell. It basically switches the immune cell off to avoid detection.

              Researchers at the Fred Hutchinson Cancer Research Center in Seattle have investigated a new drug called Avelumab that acts as a sheath to cover and disable the cancer cell’s key. Now when the immune cell approaches the cancer cell, the cancer cell cannot use its key to inactivate the immune cell, and the body can effectively eliminate the cancer. Thanks to clinical trials run through the Fred Hutchinson Cancer Research center, Avelumab just received FDA approval as the first systemic therapy to treat Merkel cell carcinoma and the first treatment of any kind to treat the metastatic form of Merkel cell carcinoma.

              Both of these emerging modes of treatment address the two questions posed earlier. Targeted therapy and immunotherapy are showing great promise in more effective treatment of cancer without the nasty side effects of traditional chemotherapies. As the clinical trials continue, our refinement of these techniques will only get better, and that’s reason enough to stay optimistic about the future cancer treatment.

Links and References: - CNN article on bad luck mutations - ScienceDaily article on bad luck mutations - Scientific article on mutations (subscription required) - Scientific article on mutations (subscription required) - Scientific article on targeted therapy (subscription required) - ScienceDaily article on breast cancer metabolism - ScienceDaily article on FDA approved immunotherapy