Tag: Villanueva

Three of The Wistar Institute’s foremost melanoma researchers: professor Meenhard Herlyn, D.V.M., D.Sc.; associate professor Jessie Villanueva, Ph.D.; and assistant professor Noam Auslander, Ph.D. discussed the progress and potential in melanoma research. Each brings their own distinct expertise to the field of melanoma research with decades of combined experience, and in reflecting on the state of the field, Drs. Herlyn, Villanueva, and Auslander covered both how they came to melanoma research and how they continue to tackle the challenge of this disease every single day at Wistar.

There are a lot of cancers out there. What brought you to melanoma?

Dr. Noam Auslander: As someone who works on the computational side of things, I was attracted to melanoma research mainly because of the quantity of data. In science generally but in computational science in particular, more data is better — because that allows researchers to design high-fidelity models, which, with cancer, can lead to all sorts of benefits, like predictions of who will respond to what therapy, or which genetic patterns are implicated in a cancer.

I can access and analyze melanoma data in large batches simply because there’s a lot of it. Part of that is because it’s a common cancer — which isn’t a good thing — but because it’s both common and a subject of study for more than 40 years, that allows my team and I to improve our models.

Dr. Jessie Villanueva: For me, melanoma research began as pure scientific interest. Melanoma is an aggressive cancer, and when I started as a postdoctoral fellow, there were no approved targeted therapies or immunotherapies; if chemotherapy, radiation, and surgery all failed, there really weren’t other options.

That problem attracted me to the field as a scientist who wants to solve problems, and shortly afterward, the professional interest became a personal one: a childhood friend whom I’d known since kindergarten was diagnosed with melanoma, and not long after that, so was my uncle. Unfortunately, my uncle passed away, but my friend survived, and that combination of loss and hope solidified melanoma as something I wanted to dedicate myself toward working against.

Dr. Meenhard Herlyn: My story is not so inspiring. I was young — so I suppose it was something like a hundred years ago — but my boss told me to help him with a melanoma project, and that was that. But I was very lucky, because that project involved a man named Wallace Clark: a great pathologist of the disease, whose research laid the foundation for much of what we know today about melanoma. Much of his work was characterizing these melanoma cells under a microscope — a necessary first step — and thinking of stories in his mind about how they might behave. Characterizing and theorizing. So as a young scientist, I thought to myself, “we must find a way to fill in these stories with real data.” And I’ve followed that ever since.

There are other skin cancers; melanoma is just a subtype. What makes it so dangerous?

J.V.: Melanoma comes from cells that originally have an innate level of pluripotency (the ability to transform into different cell types); they have remarkable migratory abilities; and they give rise to a diverse array of cell types throughout the body. When those cells become cancerous, they are highly plastic and skilled at adapting to their environment. This plasticity also allows melanoma to evade treatment and become drug-resistant. Drug resistance is a big problem in the field; often when using drugs targeting one pathway, the tumors find an alternative pathway to exploit.

By collectively studying all the inner workings of melanoma — like its genetics (the kind of mutations it collects), epigenetics (how genes are turned on or off), and signaling pathways (controlling processes like cell growth, proliferation, and survival) — we aim to develop strategies that prevent tumors from evading treatment. We’ve made great progress treating melanoma, but tumors still develop strategies to bypass therapies. This ongoing challenge drives our relentless search for innovative and effective solutions, fueled by the hope of achieving cures and improving the lives of melanoma patients.

N.A.: Melanoma is associated with an unusually high inter- and intra-tumor heterogeneity; the mutational profile is exceptionally complex between different melanoma cells and even within melanoma cells. That’s why large-scale data analysis of melanoma with computational models isn’t just important but necessary — patterns that can help us fight this cancer exist, but distinguishing between patterns and noise both within a tumor and between tumors requires the help of advanced computational techniques.

Meenhard has talked about how we need to listen to cells, and that’s how I try to help Meenhard & Jessie’s work: by fine-tuning computer systems to listen for signals amid the chaos in cancer.

M.H.: We also have to remember that the cells that become melanoma are highly mobile by their very nature. As Jessie said, melanocytes have a certain amount of innate plasticity, which contributes to the cancer’s aggression once a melanocyte goes from normal to cancerous.

But that wouldn’t necessarily be as big a problem if it weren’t for these cells’ motility. When you have aggressive cancer cells moving throughout the body, that creates a situation that lends itself to metastasis. A skin cancer that isn’t melanoma doesn’t present as much danger because it’s probably more localized; I’m not saying that’s not serious, but a non-metastatic tumor on the skin is a lot easier to treat — at the simplest level, you just cut it off. With melanoma, once that diagnosis comes, the clock is ticking to stop the cancer before the metastatic impulse gets out of control.

More people are getting melanoma, with U.S. incidence up by more than 50% since 1999. Why do you think that is, and how can people protect themselves?

J.V.: The short answer is that we don’t yet know for sure — there are several ongoing epidemiological studies which we expect will provide clear answers. Lifestyle is a big part of it. Outdoor activity can be healthy; however, being outdoors means more sun & UV exposure. Anecdotally, since the pandemic, we’ve noticed more people spending more time outdoors. And that’s a risk factor.

We’re seeing a sharp increase in melanoma for young people, particularly young women. Cancer tends to be correlated with age — the older we get, the higher the probability of having cancer — but melanoma is the most frequently developed cancer in people in their 20s and 30s.

M.H.: I agree that lifestyle is probably a big factor in the increase in cases. Everything from tanning beds to taking a vacation to lie on the beach is going to give UV rays more opportunity to cause damage that could lead to melanoma. Sunlight feels good to everyone, but unprotected exposure is harmful. People get addicted to damaging UV because our skin secretes endorphins when exposed to UV, and that’s more reason to be cautious.

It’s true that people with less melanin in their skin are more at risk — which is why, for example, more leisure travel from countries in the Global North to equatorial regions that get more sun probably causes more melanoma overall — but everyone has skin, which means anyone can get melanoma. And that’s why awareness of exposure risk is so important.