The Melanoma Research Alliance (MRA) Foundation has awarded a $900,000 grant for research led by Dr. Roger Lo, a member of the UCLA Jonsson Comprehensive Cancer Center, to advance the understanding of mechanisms that determine response and resistance to two of the most promising therapies for advanced melanoma, the deadliest form of skin cancer.
Scientific advances in treating metastatic melanoma have led to two significant breakthrough therapeutic approaches for the disease: BRAF-targeted therapies, which selectively block key cancer-driving genes and signals, and immune checkpoint or PD-1 antibodies, which unleash the body’s tumor-fighting immune or T cells.
However, Lo noted, not everyone’s melanoma would benefit equally from these therapies, and it remains unclear how best to derive benefits from both types of therapies when one type of therapy alone fails to control metastatic melanoma.
“The successful development of therapies targeting mutant BRAF and blocking the immune checkpoint PD-1/L1 in metastatic melanoma has also revealed key gaps in our knowledge,” said Lo, an associate professor of dermatology and molecular and medical pharmacology at UCLA. “With this generous funding opportunity from the Melanoma Research Alliance, our research has the potential to help physicians deploy these breakthrough treatments with much more rationale and precision than ever before.”
Lo’s MRA-funded research brings together a team of experienced clinicians and scientists to analyze tumor tissues donated by patients treated with both immune checkpoint antibodies and BRAF-targeted therapy alone, and with the combination of both. Using state-of-the-art technologies to comprehensively profile cancer mutations and other key regulatory mechanisms of cancer, the researchers will seek to identify markers of response and resistance to PD-1 antibodies using a tumor biopsy before treatment. They will also evaluate how BRAF-targeted therapies affect responsiveness to immune checkpoint antibodies in melanoma.
Lo will serve as administrative principal investigator for the research studies. He will lead a cross-institutional collaborative team that includes Vanderbilt-Ingram Cancer Center’s Dr. Jeffrey Sosman, principal investigator, and Douglas Johnson, who will serve as young investigator.
"Dr. Lo and his colleagues have made major advances in understanding the etiology of melanoma and why some patients respond to or resist treatment,” said Dr. Kenneth Dorshkind, interim director of the Jonsson Cancer Center and a professor of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA. “This award is richly deserved and will allow him to continue his innovative studies in this area.”
Primary support for Lo’s grant is provided by the MRA Team Science Award Program, which is the centerpiece of the organization’s research funding initiative. The program seeks to foster a collaborative and cross-institutional research process by bringing together multidisciplinary teams of principal Investigators with complementary expertise. These team science projects promote transformational melanoma research advances with the potential for rapid clinical translation. The research is also supported by a MRA Young Investigator Award, which encourages early career scientists to focus their work in this field.
Additional funding for the Team Science Award is provided by Leveraged Finance Fights Melanoma, an annual event in New York City that brings together members of the leveraged finance community and surrounding industries to raise funds for MRA’s research program. The Young Investigator Award is supported by the Melanoma Research Alliance Foundation and philanthropic sources.