The Melanoma Research Alliance is on a mission to cure and prevent melanoma, a skin cancer that is diagnosed in more than 100,000 people each year and is expected to take the lives of more than 8,000 individuals in 2024.1 We invite stakeholders across all fields, including medicine, science, and industry, as well as patients and patient advocates, to join us in advancing research to answer key scientific questions across the four high-priority areas outlined here: rare melanomas; treatment-resistant melanomas; brain metastasis and leptomeningeal disease; and prevention and early intervention.
Marc Hurlbert, PhD
Changing the Trajectory of Late-Stage Melanoma
The rapid, paradigm-changing treatment advances in melanoma over the past decade ushered in an era of incredible advances and additional treatment options that have saved countless lives. They include the U.S. Food and Drug Administration (FDA) approval of the first immune checkpoint inhibitors, including ipilimumab, pembrolizumab, and nivolumab, and the first FDA-approved therapies targeting BRAF gene mutations and the MAPK pathway in melanoma, including vemurafenib, dabrafenib, and trametinib.
Since 2011, the FDA has approved 17 new treatments for melanoma,2 which have allowed thousands of patients with late-stage disease who once faced a grim prognosis to survive and thrive. In addition, not only are patients with melanoma benefiting from these remarkable advances, but many of these new therapies are being used to treat patients with other types of cancers as well.
In my work at the Melanoma Research Alliance, I’m reminded of the many individuals who have been helped by these new treatment options, including Alliance supporters, board members, and ambassadors. One Melanoma Research Alliance ambassador, Derrick, stands out in my mind. He was diagnosed with advanced melanoma with metastasis to the brain and lungs. His diagnosis journey started with headaches that would not resolve with at-home pain relievers. Derrick’s remarkable story of survival, nearly a decade later, is one of several similar stories in which new treatments have changed the trajectory of disease progression and given patients—and families—a second chance at life. In Derrick’s case, the treatment was a combination of checkpoint immunotherapy and stereotactic radiosurgery, and he experienced a complete response and remains cancer-free.
Derrick’s personal journey through treatment and recovery has been filled with deep gratitude. He is grateful to the scientists and clinicians who have spent their careers in melanoma research and treatment as well as to the patients and families who participate in clinical trials to advance life-saving therapies.
We are putting the pedal to the metal—and stepping on the gas—to accelerate our investments to advance research more quickly and to help patients with metastatic disease.— Marc Hurlbert, PhD
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Four Key Areas of Research
The example of Derrick’s positive outcome sets the stage for where we are today in melanoma research. Despite the remarkable, unparalleled progress in developing new treatments for advanced melanoma, our work shows us that fewer than half of patients respond to treatment in the first-line setting. This dichotomy of those with tumors that respond to treatment and those with tumors that do not presents us with an even greater sense of urgency today than we had when the Melanoma Research Alliance was founded 15 years ago.
The stories of remarkable survival starkly contrast with the thousands of stories of lives cut short and of families losing loved ones because of metastatic melanoma that did not respond to even the most advanced treatments. So, we are not resting on our laurels or pausing to celebrate the progress made. We are putting the pedal to the metal—and stepping on the gas—to accelerate our investments to advance research more quickly and to help patients with metastatic disease. To accomplish that goal, the Melanoma Research Alliance intends to invest $100 million in melanoma investigation over the next 5 years, effectively doubling our annual investments in life-saving research, and we invite partners to join us in this effort to advance knowledge across these four scientific priority areas:
1. Rare Melanomas—Rare melanomas account for approximately less than 10% of the more than 100,000 cases of invasive melanoma diagnosed annually in the United States. Some of these rare melanomas are more common across the globe and are known to affect populations in Asia and Latin America. Unfortunately, the majority of approved melanoma treatments are not as effective for rare melanomas, and patients diagnosed with these subtypes often have a poorer prognosis.
Rare melanomas include acral melanomas, which occur on the soles, palms, and under nail beds; mucosal melanomas, which occur in melanocytes of the mucous membranes in the nasal and oral cavities and anogenital tracts; ocular and uveal melanomas, which develop in the eyes, most commonly in the uvea, or the middle layer of the eyeball (iris, choroid, or ciliary body); and pediatric melanomas.
To address rare melanomas, the Melanoma Research Alliance is not only funding research but is also partnering with academic researchers to catalog and encourage access to preclinical model systems, including available cell lines and patient-derived xenograft models required to study rare melanomas (curemelanoma.org/researchresources).1 We are also leading a prospective patient registry, the RARE Melanoma Registry,2 for patients with acral, cutaneous, or mucosal melanoma.
2. Treatment-Resistant Melanomas—Understanding why some melanomas respond to immunotherapy or BRAF-targeted therapy and why some do not is another urgent scientific priority area for the Melanoma Research Alliance. Research is already deciphering differences in tumor metabolism, the role of the tumor microenvironment, immune system function, the role of aging, and other patient-related factors (including the microbiome), to name only a few examples. Progress has also been made by ASCO luminaries and pharmaceutical companies in the sequence, order, and dosing of current treatments. Although progress in understanding treatment response and resistance is being made, more research needs to be done.
3. Brain Metastasis and Leptomeningeal Disease—Research focused on melanoma brain metastases and leptomeningeal disease has lagged behind other areas. Patients with active brain metastasis and leptomeningeal disease have historically been excluded from many of the early clinical trials. Inclusion of patients with brain metastasis has changed in recent years following FDA guidance as well as a workshop about product development for central nervous system metastases that included Melanoma Research Alliance patient advocates, as well as others from the breast, lung, kidney, and primary brain cancer communities.
4. Prevention and Early Intervention—Research in improved detection, diagnostics, and prognostics for better prevention and early intervention strategies for serious melanomas is also an urgent area of unmet patient need. Research is needed to develop new tools and technologies to aid patients, primary care teams, dermatologists, and pathologists to accurately detect and diagnose melanoma at the earliest stage possible while avoiding unnecessary biopsies for patients. We also have to improve diagnostic and prognostic tests to help optimize treatments, predict response, and monitor patients for recurrence.
In addition to investing in these four scientific priority areas, the Melanoma Research Alliance will continue to support hypothesis-driven translational research through its annual Request for Proposals (RFP). Issued every August, the Alliance RFP allows scientists to propose their best ideas and apply for funding across our grant mechanisms, including individual awards for new or established faculty, pilot awards for innovative ideas without a lot of preliminary data, or team science awards to foster multidisciplinary and multi-institutional collaborations.
One unique award mechanism is the Melanoma Research Alliance Team Science Academic-Industry Partnership Award. This mechanism supports academic researchers with an investigator-initiated study and an identified pharmaceutical or biotech corporate partner to apply for Melanoma Research Alliance funding as part of the grant application process. The corporate partner provides a letter of support for the project and agrees to match Alliance funds to the university through either cash or in-kind support to collaboratively advance the proposed research.
Scientists hypothesize that some of the proteins and factors involved in neurodegeneration in Parkinson’s disease might play a role in melanoma brain metastasis.— Marc Hurlbert, PhD
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Working Together to Find a Cure
The Melanoma Research Alliance has invested more than $150 million in research since its launch in 2009, supporting more than 450 research projects at universities across the United States and in 19 countries around the globe. Although Alliance-funded research plays a key role in contributing to this rapidly advancing field, fueling innovation and collaboration globally, this progress would not be possible without the patients volunteering to participate in clinical trials and the scientists and clinicians who work tirelessly to make headway in this life-threatening cancer and improve outcomes.
Progress in melanoma research depends on collaborations outside the field of oncology as well. For example, in addition to partnerships with several cancer organizations, including the American Cancer Society and the American Society for Radiation Oncology, we are also partnering with the Michael J. Fox Foundation for Parkinson’s Research. Scientists hypothesize that some of the proteins and factors involved in neurodegeneration in Parkinson’s disease might play a role in melanoma brain metastasis, and we welcome their assistance in furthering our understanding of how to effectively treat this serious complication.
However, to achieve the ultimate goal of finding a cure for melanoma, collaboration must extend beyond philanthropy and academia. It must include the continued support of the pharmaceutical industry, which is so integral to funding cutting-edge research.
In the years ahead, we aim to actively engage numerous other partners to help us rapidly advance research and quickly get more effective therapies into the hands of patients with late-stage melanomas, and other cancers, that are not benefiting from the myriad treatment options developed over the past decade. There is no time to waste. These patients and their families are depending on us.
Dr. Hurlbert is Chief Executive Officer of the Melanoma Research Alliance.
DISCLOSURE: Dr. Hurlbert serves on the advisory board of Day One Biopharmaceuticals and Pfizer and has received an unrestricted educational grant from Natera to study physician preferences and practices.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
REFERENCES
1. American Cancer Society: Key statistics for melanoma skin cancer. Available at www.cancer.org. Accessed May 7, 2024.
2. Boutros A, Croce E, Ferrari M, et al: The treatment of advanced melanoma: Current approaches and new challenges. Crit Rev Oncol Hematol 196:104276, 2024.
