The Future of Melanoma: Q&A with Martin McMahon, PhD

Q: How does the collaboration between fields affect melanoma research?

A: As you probably know, it used to be that scientists were siloed into their discipline or area of expertise. But those days, especially in cancer research, are long gone. In order to be able to make an impact on melanoma progression or therapy, there needs to be multidisciplinary teams, which allow us to understand how the disease presents, determine what the markers of potential risks are, know the available therapies and the effectiveness of those therapies in basic cell and molecular biology studies, decide what to do when the disease comes back in an advanced or metastatic state, and identify the more aggressive properties of melanoma. To paraphrase Hillary Clinton, it will really take a village of scientists and physicians to conquer this disease. Many young scientists working in a research laboratory first encounter melanoma as a bunch of cells growing in a petri dish and in mouse models. Until you actually meet the patients, however, it’s difficult to have a full appreciation of the impact of this disease on our society. 

One of the first things that I did when I came to HCI was shadow one of our melanoma surgeons, Robert Andtbacka, MD, and also one of our medical oncologists, Kenneth Grossman, MD. Through them, I met a few of our melanoma patients, which helped me put the disease into context such that I feel I have a better understanding of the disease from the petri dish to the patient. 

I also work closely with one of our dermatologists, Doug Grossman, MD, PhD. Dr Grossman sees patients with early-stage melanoma, which he resects, and he has a sense of the public health issue because of the number of patients he sees in his clinic. Dr. Grossman is interested in markers of potential future recurrence and chemoprevention. To make any headway in either area, Dr. Grossman has to not only see patients and have access to clinical specimens, but also work collaboratively on genetically engineered mouse models where he can test some of his ideas that could be useful in the clinic for preventing melanoma development or recurrence in high-risk patients.

At HCI, we have a melanoma treatment planning conference every Thursday morning where we talk about individual patients, how their disease manifests and genetic abnormalities, and discuss and make recommendations for particular types of treatment. In that room on a Thursday morning, there are PhD students, postdoctoral fellows, and basic science faculty, all of whom are keen to understand what the clinical picture looks like and are interested in contributing their knowledge to the treatment of melanoma in its various forms.

Many places have something like this that allows physicians, scientists, faculty, students, and fellows to rub shoulders with one another, which I believe is the way that clever ideas percolate up from the lab to the clinic and back again. This is how science works best, in my opinion. The scientists in the trenches in the lab who are doing the experiments often have the brightest ideas and in order for those ideas to see the light of day it is important for them to interact with other scientists, physicians, patients, and people across the entire spectrum of melanoma research, melanoma clinical care, dermatology, etc. 

If we seek to make an impact on this disease all the way from the bench to the bedside it will take a concerted effort by teams that include dermatologists, biochemists, geneticists, molecular biologists, pathologists, surgeons, oncologists, and radiologists.  

Dr. McMahon and colleauge

Figure 1. Martin McMahon, PhD, speaking with a colleague in his laboratory.

Q: Is it important for dermatologists to have a basic understanding of genetics and immunology?

A: Absolutely.  These days, academic dermatologists cannot avoid the importance of genetics and the role of the immune system in treating patients with melanoma. At HCI, dermatologists tend to see the earliest stages of melanoma—melanoma in situ on the skin. When the melanoma becomes more advanced, it often becomes a question for oncology as opposed to dermatology, even though dermatologists will often be involved in those decisions. 

Nonetheless, academic dermatologists interested in melanoma cannot escape basic science, whether it be the basic science of genetics, the basic science of cell and molecular biology, and, now with the advent of immunotherapies, at least a rudimentary understanding of the immune system. 

When a patient with a pigmented lesion that is diagnosed as melanoma shows up in a clinic to see a dermatologist, he or she is going to have a whole bunch of questions: What is the genetic subtype? Am I cured, or should I be constantly vigilant about the possibility of it coming back? What sort of treatment should I receive now? If the disease comes back, what are my treatment options in the future? In order for academic dermatologists to answer patients’ questions, they need to have some knowledge of each of these areas, especially now that patients can find a lot of this information online. 

While improving patient care is the responsibility of dermatologists, oncologists, and surgeons, I think collaboration between scientists and physicians is crucial for understanding how to best treat patients with melanoma. If our aspiration is to get to the point where we can actually cure, or at least put into very prolonged remissions, patients who have advanced melanoma, then there needs to be a functional interaction between scientists and physicians. For example, getting something as simple as patient specimens that can be used in the laboratory requires the engagement of surgeons and pathologists performing biopsies in order to collect those specimens. Equally, it is essential for scientists in the lab who are researching combination therapies, such as pathway-targeted therapies or immune-oncology agents, to have a physician who is interested in translating that information from the bench to patients in clinical trials. This is true for almost every type of cancer, but melanoma in particular because in many ways melanoma is the poster child for several therapeutic approaches and also the poster child for an almost entirely 100% preventable cancer. 

Melanoma is in the vanguard for understanding cancer risk and prevention, including chemoprevention, early stage predictions, and prognostications for those who are at risk for advanced disease or recurrent disease, and numerous therapies. For a disease that, overall, does not kill that many people in the United States compared with other cancers, it has had an outsized impact on the development of novel cancer therapies. Our understanding of how melanoma develops and how melanoma can be treated relies on a collaborative back and forth between scientists working in the research laboratory and physicians who are seeing patients in the clinic.

Another thing I would like to mention that epitomized the field and continues to epitomize the field is the international collegiality and collaboration between researchers and physicians in the melanoma community. I think this is really special and makes it a very special environment in which to do research. Possibly because it is a somewhat small community, most people in the field know one another. When I came into the melanoma world, I had never worked in melanoma, but many people already in the field welcomed me and the members of my laboratory, and other basic scientists, with open arms because they felt that we could bring knowledge and expertise that might ultimately be useful for patients, particularly those in the clinical community. This was also true for the development of immunotherapy, which was pioneered by Dr. Jim Allison who was recently awarded the Nobel Prize for his pioneering groundwork in this area, much of which was focused on melanoma.  

Q: Do you have any final comments you would like to share?

A: I have worked in the melanoma field for maybe 10 or more years now and I find it to be completely compelling area of research. The cell that gives rise to melanoma, the melanocyte, is one of the most interesting cells to study in the body. I find it fascinating to learn about melanocytes, pigment production, and the conversion of normal cells into aberrant melanoma cells, which is a disease that is finally beginning to come within our grasp because of our knowledge of genetics, biochemistry, cell biology, and therapeutics. It has been a remarkable time to be in the field, and I continue to look forward to future advances in melanoma that will prevent the disease from happening in the first place and allow patients with advanced melanoma to receive regimens of care that would either cure them or put their disease into prolonged remission. There is an incredible level of optimism in the field and we have made remarkable strides, but there are still many challenges to be addressed before we can claim some measure of victory against this disease. n

Reference

1. Das Thakur M, Salangsang F, Landman AS, et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature. 2013;494(7436):251-25.



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