8th Annual Scientific Retreat Recap

The end of February was a momentous one for the MRA team and all the folks in the melanoma community. We hosted our 8th Annual Scientific Retreat in Washington, DC, and they truly just seem to get better and better.

The Retreat serves two main roles for those invited participants. First, is the centerpiece of scientific knowledge sharing, as evidenced by the more than 20 MRA-funded investigators who presented at the meeting as well as several supplementary events and sessions aimed to provide a holistic look at the state of melanoma research and treatment. Secondly, the Retreat provides an opportunity for participants from all sectors to network. We consistently hear about the new collaborations to fight melanoma that arise from networking at this meeting.

Our Melanoma Forum opened the Retreat with a session about the continuing evolution of patient participation in the research process. It was attended by 50 patients, advocates, and supporters who shared their personal experiences to help advance our work by articulating the unmet needs and burden of the disease from those who understand it personally. Special thanks to Raj Kulkarni, an MRA Young Investigator at UCLA, and Kim McCleary of FasterCures for helping to build out this event.

MRARetreat_Selects-16Our lunchtime panel discussion (left), moderated by Mike Milken, featured four amazing thought leaders in melanoma. Drs. Boris Bastian of UCSF, Levi Garraway of Dana-Farber Cancer Institute, Lynn Schuchter of U Pennsylvania and Suzanne Topalian of Johns Hopkins University wo provided a look forward for the future of melanoma research.

In addition, we convened the growing group of MRA-funded Young Investigators to explore several key issues in clinical translation, while our Industry Roundtable meeting brought together representatives from the NCI, FDA, academia and industry to thoughtfully address challenges and opportunities for future collaboration on behalf of patients.

MRARetreat_Selects-19A highlight of the meeting was welcoming newly appointed FDA Commissioner Robert Califf (left), who came straight from his confirmation at the White House to deliver remarks to the MRA community.

It was truly a convergence of the brightest stars in the field and a community dedicated to achieving MRA’s mission of defeating melanoma. You can read more about in blog posts from Dr. Len, of the American Cancer Society, and T.J. Sharpe, a melanoma survivor who blogs for Philly.com.

We thank everyone who came to participate in the meeting, as well as our sponsors, who all helped make our 8th Annual Scientific Retreat a success!

 

 

Gearing up for our Annual Scientific Retreat

The Melanoma Research Alliance’s (MRA) annual Scientific Retreat brings together hundreds of scientists, industry professionals, and patients from around the globe to foster collaboration in the field of melanoma research. This year, MRA will host its eighth retreat from February 24-26 in Washington, DC.

This year’s scientific sessions begin with a discussion on potential new therapy targets. Scientists from a variety of institutions, including Duke University and Sheba Medical Center in Israel, will discuss advances in the fields of targeted therapy and immunotherapy. In addition to discussing therapies, a prevention-focused afternoon session will address the pros and cons of mandatory skin screening and the self-screening process.

In efforts to include the expanding role of patients in the research process, this year’s Retreat will include a Melanoma Forum geared toward patients, caregivers, advocates and supporters. Moderated by FasterCuresKim McCleary, patients will be invited to an interactive discussion on their active involvement in research. The forum will provide an excellent venue for patients to engage in discussion and meet other individuals who share a common goal for the future of melanoma research.

flaherty, sigal, topalian

Participants at the 2015 MRA Scientific Retreat

The MRA team is excited to host this extraordinary group of individuals under one roof. Our Chief Science Officer, Louise M. Perkins, Ph.D., is looking forward to seeing so many close colleagues and friends from the melanoma research sphere. “There’s no event quite like this to share the latest in research and to build new collaborations.”

Tasheema Prince, Scientific Program Manager, joined MRA in 2015, and is anticipating her first retreat. “It’s essentially a glimpse into the collective fight to end melanoma and I’m very excited to witness a convening of bright scientific minds in the field,” explains Prince.

We hope the retreat allows individuals to build valuable relationships and accelerate momentum in the field of melanoma research, and ultimately help more patients overcome this disease.

To get more details on the Scientific Retreat visit our website to see a draft agenda and learn more about the event.

Identifying Melanoma as a Single Cell

A recent study published in the journal Science could provide important clues for melanoma diagnosis.  Led by Leonard Zon, M.D., of Boston Children’s Hospital, the study looked at cancer in zebrafish from the very beginning – when it starts as just a single cell.

Funded in part by MRA, the study is the first to see melanoma – or any other cancer – begin this early. The researchers found that the cancer developed from an interesting process: the cells reprogrammed back to an embryonic state.

“The process was surprising to us,” noted Dr. Zon. “The melanoma essentially reprogrammed melanocytes to a stem cell, similar to an embryo’s neural crest.”

While the study looked at melanoma in zebrafish, Dr. Zon said human melanomas work similarly. Moles contain melanocytes, the pigment-producing cells. Most moles have a common genetic alteration in a gene called BRAF, but very few moles turn deadly. Understanding the early process of how and why cancers develop could help target treatments, or perhaps reveal prevention strategies.

Dr. Zon’s team used fish that had the BRAF mutation. They created a way to make the fish cells light up in bright green if the embryonic gene called crestin was turned on. The fish that lit up with the bright green signal were the same fish that developed melanomas.

“There are important implications of this work for cancer diagnosis with a newly found tumor, and potential opportunities to stop cancer before it ever begins,” explained Dr. Zon.

The new published research builds off of earlier work by Memorial Sloan Kettering Cancer Center’s Richard White, MD, PhD, recipient of the Maria and Bill Bell – MRA Young Investigator Award, who observed that the melanomas in zebrafish were derived from crestin-expressing cells. Dr. White is a co-author in this new paper.

Dr. Zon told the Harvard Gazette that these findings could not only lead to genetic tests for suspicious moles to see if the embryonic cells have been activated, but also help researchers develop treatments that could prevent a mole from becoming cancerous.

You can read more about Dr. Zon’s research in the New York Times.

Researcher Q&A: Dr. John D’Orazio

In the latest blog post, we chatted with the University of Kentucky’s John D’Orazio, M.D., Ph.D., a pediatric hematologist oncologist, and a 2015 MRA grant awardee. Read on to learn what he has to say about melanoma research and prevention efforts.

How did you get interested in melanoma and your field of research?

I am a physician scientist who combines a clinical career in pediatric oncology with basic research aimed at understanding the molecular mechanisms of melanoma development. Kids don’t usually get melanoma, thankfully. But prevention is such an important part of combating this disease – particularly during childhood since pediatric UV exposure plays such an important causative role for melanoma later in life. My overarching interest, related to pediatric oncology, is understanding cancer predispositions.

Tell me about your research.

During my fellowship, I paired up with Dr. David Fisher, who is one of top melanoma biologists in the world and who happened to also be my ward attending on the pediatric oncology service at Boston Children’s Hospital. David approached me with a research project relating to understanding why fair-skinned people get melanoma so much more than dark-skinned individuals. We knew it wasn’t just about melanin since albinos – people with normal numbers of melanocytes but who don’t make melanin at all because of inherited defects in melanin synthetic enzymes – almost never get melanoma.

In the Fisher lab, I focused on the contribution of the melanocortin 1 receptor (MC1R) in pigmentation and melanocyte UV sensitivity. We chose to study MC1R since loss-of-function MC1R polymorphisms are very common among fair-skinned people and raise lifetime melanoma risk by about four-fold. Using a unique mouse model that I developed, David and I discovered that MC1R controlled whether a mouse’s skin would express dark or light melanin.

We found that pharmacologic replacement of MC1R signaling function, through the topical application of cAMP-promoting drugs to the mice, was enough to turn the skin from a blonde UV-sensitive and cancer-prone complexion to a heavily melanized UV- and cancer-resistant phenotype instead. We had demonstrated sunless tanning by pharmacologic manipulation of the MC1R signaling axis, suggesting that skin could be shielded from UV damage by melanin stimulation.

Since establishing my own lab, we’ve focused on other ways in which MC1R signaling enables melanocytes to resist UV damage and carcinogenesis. We’ve been studying how cAMP signaling increases the efficiency by which melanocytes recover and repair UV DNA damage.

How has MRA funding helped your work?

MRA funding absolutely lets us open up a new avenue of research that wouldn’t have otherwise been possible. We’re still focused on MC1R signaling but are now funded to study the natural hormonal regulation of this pathway in the skin. The MRA grant allows us to study how the pathway impacts melanoma risk on multiple fronts.

What do you hope to see more of in the future of melanoma research?

Melanoma incidence just keeps getting higher. Whatever is underlying it, we have to do something about it. Almost 2% of the population is going to be affected by melanoma in their lifetime. It’s a big problem, and although exciting advances are being made in the field of anti-melanoma therapeutics (especially targeted therapy and immunotherapy), it is still far better to avoid the disease in the first place. I would like to see more focus put into active melanoma prevention, not only through policy and indoor tanning regulation, sun protection, and public health aspects, but by using a science-based approach to enhance the skin’s ability to resist UV-mediated carcinogenesis.

What do you do when you’re not seeing patients or conducting research?

I’m a family guy. I have one daughter, a wife who is in science, and a dog. I love to cook, enjoy nature photography and have gotten pretty good at pickleball.

 

Learn more about MRA’s Research.

 

Taking a Closer Look at MRA’s Recent Grant Funding

By Laura Brockway-Lunardi, PhDLaura Brockway Lunardi
Scientific Program Director
Melanoma Research Alliance

Recently, MRA announced the results of its latest round of grant-making, enabling more than $13 million of melanoma research. The awards, which include a total of $7.6 million from MRA’s research funds and $5.7 million obtained through the organization’s collaborative funding program, will support:

  • 34 projects
  • 43 Principal Investigators (PIs)
  • 26 academic institutions in 4 countries

With this latest round, MRA has awarded almost $68 million to 237 PIs at 99 institutions in 14 countries since its founding in 2007. These awards aim to:

  • advance the understanding of melanoma risk factors
  • identify new therapeutic approaches
  • develop biomarkers that lead to the improvement of existing treatments

Expanding the Pool of Melanoma Researchers

One of the goals of MRA is to not only fund the best and brightest melanoma researchers but also bring new investigators into the field. We are meeting this goal: every year, at least two-thirds of awarded PIs have not received previous funding from MRA, equating to 20 to 30 new PIs per year. At least six new institutions are brought into the MRA program each year. MRA-supported Young Investigators (through Young Investigator Awards and Young Investigators on Team Science Awards) now number 73 strong, and we’re on track to fund at least 80 of these early career scientists by 2017.

Focus on Melanoma Treatment

In addition to growing human capital, this new round of awards also strengthens MRA’s emphasis on treatment science, bringing MRA’s investment to more than $60 million (or 89% of funding) to date to accelerate new tools and treatments to patients with metastatic melanoma. MRA’s research portfolio has supported studies of 48 unique therapeutic approaches, including research on all of the melanoma therapies approved since 2011. MRA’s portfolio includes 21 supported clinical trials that incorporate correlative studies of treatment response and mechanistic studies.

2015 continues the remarkable momentum in clinical advances with new drug approvals and additional agents in late-stage clinical development. Unfortunately, not all patients will benefit from these new treatment approaches and more research is needed to identify new drug targets and biomarkers. Many of our newest awards are focused on just this, and include research on new genetic and epigenetics drivers of melanoma, as well as novel approaches in immunotherapy.

In addition, improving upon currently available therapies through research on combinations of agents and biomarkers is needed to maximize the existing anti-melanoma arsenal.

One such study of combination approaches joins MRA in collaboration with the Rising Tide Foundation for Clinical Cancer Research and the Tara Miller Melanoma Foundation to support clinical and translational research on immune checkpoint blockade combined with radiation therapy through a Team Science Award led by Robert Vonderheide at the University of Pennsylvania.

Addressing Unmet Needs

The latest awards also address critical areas of unmet need, including developing new approaches to treat patients with metastases to the central nervous system (brain and meninges). For example, a Bristol-Myers Squibb-MRA Team Science Award led by Ryan Sullivan at Massachusetts General Hospital will conduct a clinical trial to study the activity of ipilimumab and nivolumab in patients with leptomeningeal metastases.

Through Established Investigator Awards, Timothy Bullock at the University of Virginia will determine if focused ultrasound technology will increase the effectiveness of immunotherapies, and Sheri Holmen at the University of Utah will study key proteins implicated in promoting brain metastases and determine targeted treatment approaches against them.

These are just a few examples of the cutting-edge research programs that comprise our most recently awarded programs, none of which would be possible without the support of our donors and partners, which include a growing list of institutions, foundations, and companies that share our common goal of defeating melanoma.

Planning for 2016 Grant Funding

As we wrap up the 2015 cycle, planning for our 2016 cycle is well underway. We hope to announce our next Request for Proposal in early September, and we anticipate another competitive pool of applicants who will continue to push forward in our quest to understand and eliminate death and suffering from melanoma.

The Latest in Melanoma Research: News from the Two Biggest Cancer Meetings

By Louise Perkins, PhD
Chief Science Officer

There’s been a lot of news on melanoma treatments in the last couple of weeks coming out of the two largest cancer conferences held each year: the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) annual meetings. The results – particularly in the area of immunotherapy – really are exciting for the field of melanoma and cancer, at large.  On the Diane Rehm Show this week, melanoma was described as the “poster child for immunotherapy,” which it certainly has been.

So what’s new, and what does it mean now and for the near future?

Melanoma drugs circa 2014

In September and December 2014, two new melanoma treatments were approved by the FDA for advanced metastatic melanoma. These are the anti-PD-1 drugs pembrolizumab (pembro, Keytruda®) and nivolumab (nivo, Opdivo®). Pembro and nivo release the so-called “brakes” on the immune system, to help the body’s own immune system fight cancer. Another drug, ipilimumab (ipi, Yervoy®), is an anti-CTLA-4 drug and was FDA-approved in 2011.  Check out our video that describes how these immunotherapies work.

The latest news from early 2015
Researchers have been trying to answer a few important questions about these new immunotherapies, such as:

  1. Is anti-PD-1 (pembro, nivo) treatment better than anti-CTLA-4 (ipi) in patients who have not had any prior therapy?
  2. Do anti-CTLA-4 and anti-PD-1 in combination work even better than either treatment alone for patients who have not had any prior therapy?

MRA-funded investigator Jedd Wolchok, MD, PhD, and colleagues addressed the latter question in a Phase 3 trial at ASCO. The study involved more than 900 previously untreated metastatic melanoma patients and compared three different therapies:

  1. Ipi alone
  2. Nivo alone
  3. Ipi and nivo in combination

They found that nivo either alone or in combination with ipi had better results for patients than ipi alone.

This is similar to what was reported at AACR by Antoni Ribas, MD, in a Phase 3 study of the other anti-PD-1 drug pembro, which showed that pembro was better than ipi in previously untreated patients.  More trials are underway to confirm whether or not the combination allows patients to live longer (overall survival) versus single-agent therapy.

One important piece to note is that recent studies found that the increased benefit of the combination also comes with increased side effects; in fact, approximately one-third of patients discontinued therapy due to side effects.

At ASCO, Michael Atkins, MD, summarized these clinical findings that have been presented over recent months:

  • Nivolumab is better than ipilimumab alone
  • Pembrolizumab is better than ipilimumab alone
  • Nivolumab and ipilimumab in combination are better than ipilimumab alone

What does this mean for melanoma patients?

Believe it or not, things are moving amazingly fast. So what does all of this mean for patients in June 2015, just 9 months after the first anti-PD1 treatment was approved by FDA?  Well, one leading cancer guideline group, the National Comprehensive Cancer Network, already updated its melanoma treatment guidelines in March to recommend that oncologists consider a single-agent anti-PD1 (either nivo or pembro) as first line treatment for advanced metastatic melanoma patients (pembro and nivo were FDA approved for patients who have progressed on prior therapies).

More research is needed to determine if and when and for which patients the combination of anti-PD-1 and anti-CTLA-4 should be used.

Why We Stand Up to Melanoma

By Wendy Selig, MRA President & CEO

SU2C 2014 wendy selig and ryan selig

Wendy Selig with her son Ryan

It might have been easy to get caught up in the glitz and glamour of a star-studded Hollywood event this past week in LA as Stand Up To Cancer held its latest prime-time broadcast in support of cancer research.   After all, some of us had the chance to enter the historic theater via a red-carpet lined with paparazzi.  And during the show itself, every few minutes for the entire hour a different A-list celebrity appeared on the stage.

But there was something much more personal and powerful going on in that room where celebrities were coming together with cancer researchers and doctors, foundations, corporations, patients and their families.  It was the sense of hope and promise that these cancer survivors brought to the event that made it most impactful.   Their courage, resilience and resolve is what inspires me most.  The evening really brought home just how important it is for all of us to work together in collaborations that will defeat cancer in all of its forms.

I was fortunate to be there on behalf of the Melanoma Research Alliance (MRA), saluting the life-saving work of our MRA-SU2C Melanoma Dream Team and the Melanoma component of the CRI-SU2C Immunology Dream Team.  These brilliant scientists and physicians have dedicated their professional lives to understanding how melanoma works and designing ways to stop this deadly killer in its tracks.

It was an honor to meet one of the melanoma patients profiled during the broadcast – a lovely woman named Kathy whose doctor, Toni Ribas from UCLA, is an MRA-funded investigator and member of our Medical Advisory Panel.   Despite having been extremely sick as a result of her cancer just months ago, Kathy is now back to living her life, thanks to the exciting progress that has been made in delivering new immunotherapy treatments.  Kathy’s strong desire to be there for her children and new grandchild, brings home the promise and hope we all feel as a result of recent progress, including new therapies like the anti-PD-1 therapy approved just last week by the FDA.

But even with all of the good news coming in the melanoma field, we know that our work is far from finished.   For every story like Kathy’s, there are still too many stories of people who are suffering from this beast.  As I write this, we have just learned of the tragic loss of a young woman named Jackie to this terrible disease.   She was only 22 and, though she fought with such grace and courage for more than two years, she passed away this week.

And that’s why MRA, working with our partners at Stand Up To Cancer and dozens of other allies across sectors, won’t rest until we’ve arrived at the day when no one suffers or dies from melanoma.  That’s why we’ve just launched our next Request For Proposals soliciting high-impact projects from researchers around the world.   We plan to fund at least $7 million in our next grant cycle, building upon the $60 million we’ve already invested.  And that’s why we seek to engage more people in our mission through alliances and collaborations to fund more life-saving research to accelerate progress toward cures for melanoma.

About the Author

Wendy Selig 2013Wendy K.D. Selig is President and CEO of the Melanoma Research Alliance (MRA), a public charity focused on finding and funding the most promising translational melanoma research worldwide that will accelerate progress toward a cure.  Ms. Selig drives and manages MRA’s strategic priorities, research portfolio, engagement with more than 90 corporate and non-profit Allies, and day-to-day operations. MRA, founded by Debra and Leon Black under the auspices of the Milken Institute, is the largest private funder of melanoma research.