Researcher Q&A: Dr. Neil Ganem

In an effort to share more about the work being done in the field of melanoma research, we are beginning a new feature on our blog to showcase some of our funded investigators. Today we’re talking with Neil Ganem, Ph.D., Assistant Professor of Pharmacology and Medicine at Boston University School of Medicine and recipient of the Jackie King-MRA Young Investigator Award.

Neil Ganem. Photo courtesy of Boston University School of Medicine.

Neil Ganem. Photo courtesy of Boston University School of Medicine.

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

My lab studies the causes and consequences of a phenomenon known as chromosome instability, which is a hallmark of solid tumors, including melanoma. Normal human cells maintain all of their genetic information on 23 pairs of chromosomes. By contrast, a common feature of human cancer cells is that they possess an abnormal number of chromosomes, a state known as aneuploidy. Though already abnormal, many aneuploid cancer cells continue to shuffle their chromosome content, often gaining and losing chromosomes with each cell division. This trait of cancer cells is termed chromosome instability (CIN).

CIN is known to facilitate tumor initiation, progression, the development of chemo-resistance, and relapse. Consequently, patients with CIN tumors have a poor clinical prognosis. One major focus of my research program is to uncover the cellular defects that generate chromosome instability in human cancer cells. Several years ago a colleagues of mine, Craig Ceol, generated a transgenic zebrafish model to expresses oncogenic BRAF specifically in melanocytes. Interestingly, Craig and I found that oncogenic BRAF, which is one of the most common causes of melanoma, acted as a potent driver of chromosome instability. My lab is now attempting to define the mechanisms through which oncogenic BRAF promotes abnormal chromosome segregation and CIN. To do this, we are using highly sophisticated microscopic techniques to visualize individual chromosomes as they separate during cell division.

How can your research make a difference to melanoma patients? 

A major focus of my group is to identify whether chromosome instability generated by oncogenic BRAF represents a point-of-weakness that can be therapeutically exploited. My lab has recently developed an innovative screening approach to comprehensively identify the proteins and molecular pathways required for chromosomally unstable cancer cells to survive and proliferate.

Ultimately, our long-term scientific goal is to develop new strategies to specifically inhibit the growth of abnormal, chromosomally unstable melanoma cells while sparing the normal cells from which they originated. We hope that by targeting chromosome stability, rather than a specific oncogene, we may ultimately develop new and innovative treatments for melanoma patients.

How has MRA funding helped your work?

The Jackie King Young Investigator Award from the MRA is supporting the salary of Sanghee Lim, an M.D./Ph.D. student in my laboratory. Sanghee is a fantastic student who has already finished his first two years of medical school. He will now spend the next four years earning his Ph.D. in my lab before completing his final two years of medical training. Sanghee is interested in pursuing a career in oncology/dermatology. This is one of the long-reaching effects of the support from the MRA: Awards provide the financial support to engage young M.D./Ph.D. candidates in projects directly relevant to melanoma, which may ultimately influence those students to make melanoma research their career ambition.

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

As the father of three young boys, I spend most of my free time doing dad stuff! I spend a lot of time at playgrounds, playing sports and games, and building Legos. When I have time to myself, I really enjoy yard work and doing projects around the house. I used to enjoy playing hockey, but it’s been so long since I last played that I guess I should consider myself retired at this point.

Learn more about Dr. Ganem and all the MRA Young Investigators.

Immunotherapy for Melanoma: Where We Are

As was reported last week, Former President Jimmy Carter has melanoma that has spread to other organs, and part of his treatment will include an immunotherapy drug. Immunotherapy is a term used to describe treatments that harness the body’s immune system to fight cancer cells. Several of these are approved by the FDA for treating melanoma, including the one Mr. Carter is getting, and newer ones are in the pipeline.

How Does Immunotherapy Work?

Using your immune system to fend off cancer sounds natural and appealing, right?  After all, the immune system helps to combat other diseases like infections, so why not cancer, too? Doctors have been trying for decades to take advantage of the ability of immune cells to distinguish between healthy normal tissue and diseased cancer tissue. Unfortunately, only recently has this worked well in cancer.

It turns out that in patients with melanoma, component cells of the immune system have been fooled into ignoring the melanoma. How does this happen? Certain molecules act as “checkpoints” to prevent attacks on healthy cells and turn off a potentially over-eager immune response to minimize autoimmune disease (when the body attacks and destroys healthy body tissues by mistake). Melanoma cells take advantage of this regulatory step and turn on checkpoint signals that let them avoid being detected by the immune system. It’s like Harry Potter and his cloak of invisibility or Klingon Warships with the same…pick your metaphor. The melanoma cells subvert checkpoint signaling to essentially become invisible and avoid being killed by the immune system.

A truly profound change in recent years is the advent of certain immunotherapy drugs that target and block these checkpoints, which increases your body’s immune response. Without the checkpoint signal, the immune cells can do their job of recognizing the tumor as foreign. In this way, immunotherapy drugs activate the immune system to invade tumors and attack melanoma cells.

Patients receive checkpoint inhibitor immunotherapy drugs intravenously (into a blood vein). They are systemic, which means that the treatments travel through the bloodstream to reach all parts of the body. Cancer physicians use systemic immunotherapy to treat metastatic cancer, which is cancer that has spread from its original location to other areas of the body.

What Immunotherapy Drugs are Used for Melanoma?

Since 2011, the U.S. Food and Drug Administration (FDA) has approved three immunotherapy drugs:

  • Yervoy® (Ipilimumab),an anti-CTLA-4 antibody, approved in 2011
  • Keytruda® (Pembrolizumab), an anti-PD-1 antibody, approved in 2014
  • Opdivo® (Nivolumab), an anti-PD-1 antibody, approved in 2014

The anti-PD-1 immunotherapy drugs in particular are showing promise for other types of cancer, too. In fact, earlier this year, the FDA approved nivolumab to treat a certain type of lung cancer.

What’s Next for Immunotherapy Drugs?

The approvals of these immunotherapy treatments have come at an amazing pace and along with targeted therapies the melanoma treatment landscape is dramatically improved compared to just 5 years ago. Unfortunately, the current treatments don’t yet offer a universal cure. The gains are significant and unprecedented – make no mistake.  But some tumors are resistant to treatment and new approaches must be developed to overcome the limitations.

Now, researchers are trying to understand how to tailor the treatments to maximize results for more patients. And history teaches us that using active drugs in unique combinations often works well in cancer. So, some of what we’re trying to understand now include questions like:

  • What are the optimal combinations that balance good activity and good tolerability
  • What is the best order to give these therapies to patients
  • How long should patients be treated for the best results
  • Which patients will most likely benefit from certain drugs or combinations

The European Commission recently approved nivolumab and pembrolizumab for treatment of patients with advanced metastatic melanoma, including in the first-line treatment of the disease. In the US, the FDA is considering this same indication for each drug, as well as the combination of nivolumab and ipilimumab. FDA decisions are expected by the end of 2015.

With anti-PD-1 drugs first approved just last year, these expanded uses clearly demonstrate the remarkable pace of advances for melanoma patients around the world and the hope for even better outcomes for patients in the months and years to come.

What We Can Learn from President Carter’s Melanoma Diagnosis and Treatment

By Louise M. Perkins, Ph.D.

Chief Science Officer

President Jimmy Carter revealed to the world his diagnosis with melanoma with both the grace and bravery that we may all aspire to in the face of such news. His melanoma presentation was a bit unusual and naturally confusing. He was initially diagnosed with a tumor in his liver and then on closer exploration it was found to have spread to the brain. Once the tumor in his liver was removed and analyzed, his doctors could tell that it was a melanoma. Understanding what type of cancer he has is important, as it is helping to direct his treatment. It is fairly typical for melanoma to progress to the brain, as has been reported in President Carter’s case.

Image courtesy of cancer.gov

            Image courtesy of cancer.gov

So, how can a cancer that usually starts in the skin suddenly pop up in someone’s brain and liver?  Well, first of all, this is really rare. Some estimates say only 2% to 6% of melanomas are identified without ever finding the original (primary) tumor. Where do these odd melanomas come from?

Let’s back up a second. Melanomas are pigment-producing cells called melanocytes that have become cancerous.

Melanocytes are not only present on what we think of as skin, but also found in mucosal surfaces like the inside of the nose or mouth, under nails, as well as in eyes and ears – and even some organs.

So, in the case of President Carter, there are a couple possibilities:

  1. He may have had a skin melanoma that had a couple bad cells that split off and hid while his immune system effectively dealt with the primary tumor and he was none the worse. For whatever reason the stray cells then got out of control, leading to his current disease.
  2. Alternatively, something similar may have happened with the melanoma being relatively benign at a rare site in his body, but a few “bad guy” cells broke away and seeded in the brain and liver and then grew more aggressively.

We may never know.

The good news is that Mr. Carter is able to take advantage of the benefits of research that has led to sweeping advances in melanoma. Beginning in 2011, care for patients with advanced melanoma changed profoundly and the FDA has approved eight new treatments since then. Of relevance to President Carter’s specific treatment plan, MRA has funded research on melanoma brain metastases as well as on the combination of anti-PD-1 treatment and radiation therapy, similar to what has been offered him by his doctors.

MRA’s critical and timely infusion of funding has contributed to the sweeping changes in melanoma care with a significant part of our portfolio invested in research on just the types of treatments that will hopefully help President Carter and tens of thousands of other cancer patients in the future. My thoughts and prayers are with him and the many others engaged in their fight against melanoma.

You can learn more about our investments and hope you will consider making a donation to continue to support melanoma research.

A Conversation with Board Member Jami Gertz

We’re featuring an interview with MRA Board Member and actress Jami Gertz on our blog. This was repurposed, with permission, from the blog of our partners at Neiman Marcus

JAMI GERTZNM: How did you get involved with Melanoma Research Alliance?
JG: My sister-in-law, Debra Black, founded Melanoma Research Alliance (MRA) with her husband Leon, after her personal battle with melanoma. During the early days after her diagnosis, we were all shocked to learn just how few treatments were available – and how little progress had been made over the years. Debra and Leon’s passion for advancing treatment options for melanoma patients led to the creation of MRA. I’m so proud of Debra and thrilled to be a board member.

NM: What are the greatest challenges that MRA faces with the rise of melanoma and the survival for those with advanced disease remaining static?
JG: There have been tremendous advances in treatment for melanoma in the last five years, including many new FDA-approved drugs. There has also been a lot of media attention about immunotherapy and personalized medicine for cancer treatment, which is really fantastic. But there is still a lot that we do not understand about why certain treatments work for some people and not for others. We have to keep working to ensure that we’re doing the best we can for patients with this terrible disease.

NM: How is MRA addressing these challenges?
JG: What’s unique about MRA is that thanks to Debra and Leon’s ongoing support, 100% of donations go directly to research. MRA has provided more than $60 million for melanoma research worldwide. The organization fosters collaboration among multiple stakeholders, bringing together researchers, the pharmaceutical industry, foundations, donors and patients to help accelerate progress toward finding treatments and hopefully a cure.

NM: Describe some of the ways in which we can protect ourselves from the sun’s damaging rays?
JG: One of the easiest things we can do is to wear sunscreen every day. It should be part of your daily routine, all year round. It’s also good to cover up with hats, UPF clothing and sunglasses. Fortunately, there are many new brands that are blending fashion and sun safety quite well.

NM: How has social media affected public awareness of melanoma?
JG: Social media can be an agent for good, and it plays an important part in melanoma awareness because melanoma is the second most common cancer among young men and women. My hope is that we can continue to share information about the dangers of melanoma so that everyone knows how important prevention and early detection are for survival.

NM: What is the biggest misconception about melanoma?
JG: I think people have a tendency to downplay the seriousness of melanoma and think it can be easily treated. While other types of skin cancers have lower death rates, melanoma is very serious and has the highest death rate of all skin cancers. And while genetics may increase your chances of getting melanoma, we know that exposure to UV rays is a major risk factor for this disease.

NM: How can we improve early detection?
JG: One way we can improve early detection is to really know your skin. Perform monthly skin checks to look for changes to your moles or freckles. If you’re familiar with your skin, you’re more likely to spot a change early.

NM: What is the most rewarding aspect of your work with MRA?
JG: MRA is truly making a difference for people with melanoma. In the last five years, there have been eight drugs approved for melanoma treatment, which is more than in the previous 30 years combined. It’s providing hope for patients with melanoma, and it’s also showing promise for patients with other types of cancers.

NM: What motivates you to continue to fight for this cause?
JG: My sister-in-law courageously battled melanoma and has poured so much of her time and resources into this very personal cause. She is my biggest motivation.

NM: I hope to one day…
JG: Live to see a time when we have found a cure for everyone suffering from melanoma.

Join Us in Helping Americans Stay Sun Safe This Summer

Today’s blog post is from our partners at Lands End. See how they are joining the fight against melanoma – and how you can get involved.

Skin cancer is the most common form of cancer in the United States and Lands’ End wants to keep your skin safe!

We are proud to announce our support of the Melanoma Research Alliance (MRA) to aid their mission of accelerating research, advancing cures, educating and preventing new cases of melanoma. We understand the importance of sun safety and we are committed to providing quality products that can help safeguard you from the sun’s harmful rays and that offer effective UPF 50 protection.SunSavvy

In June the CDC released a new study stating that melanoma rates have doubled in the last thirty years – at a time when cancer rates have dropped overall.  In the United States, one person dies of melanoma every hour, every day.  But when caught early, melanoma is highly curable. Prevention is key.

The Melanoma Research Alliance is the largest private funder of melanoma research. MRA was founded in 2007 under the auspices of the Milken Institute, with the support of Debra Black, a melanoma survivor, and her husband, Leon.  Thanks to the generous support of its founders, 100% of donations to MRA support melanoma research.

To join our efforts, we encourage you to purchase a Lands’ End exclusive Melanoma Research Alliance monogrammed canvas water-resistant base tote with beach essentials including two UPF 50 swim tees recommended by the Skin Cancer Foundation, an all-cotton terry beach blanket, and an embroidered scarf. If you already own these items, please consider giving these totes as a gift or donating them to the organization of your choice. They’re perfect for silent auctions, fundraisers and door prizes, and 10% of the monogram tote proceeds will be donated to MRA*.

While you are out enjoying the summer with your family, we want to encourage you to stay sun safe! We have only a limited number of totes available, so please order soon at www.landsend.com.

Help us spread the word and raise money on social media too!

*Offer void in the following states: Massachusetts, Alabama, South Carolina, Illinois, Hawaii, Mississippi. The MRA name and logo are used with its permission which in no way constitutes an endorsement, express or implied, of any company or product.

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.

Sports Authority Helps to Shine Some Light on Melanoma

By Jennifer Engel

Development Manager, Foundations and Campaigns

In recognition of Melanoma Awareness Month in May, Sports Authority deployed its fifth in-store donation and consumer awareness campaign to raise money for MRA’s research program and to educate customers on ways to reduce their risk of melanoma. Throughout the month, shoppers had the opportunity to round their purchase total up to the nearest dollar, with the remaining cents going directly toward melanoma research.

In just 31 days, Sports Authority customers at approximately 460 stores in the United States and Puerto Rico raised an incredible $278,000, which brings the retail chain’s total fundraising over five years to nearly $1.2 million to support melanoma research. Stores also housed important educational information about the risks associated with melanoma and recommendations on how patrons can protect their skin.

As one of the largest nationwide sporting goods retail chains, Sports Authority is in a unique position to raise the profile of MRA and its mission while encouraging the sale and use of sunscreen and sun-protective clothing.

We at MRA are thankful for the hard work of the Sports Authority leadership and corporate team as well as the store managers and cashiers across the nation who are the drivers of the campaign’s success. Engaging consumers—especially those drawn to active, outdoor lifestyles and recreation—in understanding the real dangers of melanoma and soliciting their support in the cause are essential to preventing new cases of melanoma.

The Sports Authority campaign is one of several MRA corporate fundraising programs in 2015. Through our alliances with companies, we’re able to amplify our reach to broader audiences with messages about the sun’s damaging rays, the importance of daily sunscreen use, and the need to be aware of changes in one’s skin.

The Centers for Disease Control and Prevention recently released data about melanoma, and melanoma rates are expected to continue to rise. The need for awareness, prevention, and research to learn more about this disease is urgent.

Thanks to collaborations with partners like Sports Authority, and the support of our founders, MRA can continue to dedicate 100% of donations to our research program to develop better prevention, diagnostic and therapeutic approaches to combat melanoma.