Melanoma research has been gaining a lot of momentum through a number of recent US FDA approvals and Orphan Drug Designations for highly promising, novel treatments for this fatal type of skin cancer. One of the new grants is the National Cancer Institute‘s Special Program of Research Excellence (SPORE) grant, which has been awarded to melanoma research efforts of an accomplished researcher at the Wistar Institute in Philadelphia.
Meenhard Herlyn, D.V.M., D.Sc. will be continuing his work on the underlying biology of melanoma using a $12.1 million SPORE grant in collaboration with a team of fellow researchers at the institute who will apply breakthrough laboratory discoveries in developing new treatments for melanoma and other forms of skin cancer. Herlyn and his team face the challenge of addressing the need for an effective therapy for late-stage, metastatic melanoma, as this type of cancer is only treatable if diagnosed early. The Wistar Institute is the first NCI-designated Cancer Center to receive a SPORE grant.
The grant will also provide the funded studies with access to 3 “cores:” 1) an Administrative Core to support the partnership between Wistar and the university, 2) a Biospecimen and Pathology Core to provide the teams with melanoma tumor samples, and 3) a Biostatistics Core to ensure accurate data analysis.
Herlyn is optimistic about ongoing melanoma research efforts as he believes the development of new therapeutics is possible through continuous, intensive basic research. With this new grant, he is confident the institute’s collaboration with the University of Pennsylvania will yield highly promising results.
Below are the details for the 4 melanoma research initiatives this SPORE grant will be funding:
1. Targeted Combination Therapy for Melanoma
Investigators: Herlyn and Lynn Schuchter, M.D. (Penn)
Targeted therapies—drugs that bind to and inhibit proteins that may cause disease—have shown great promise in melanoma, although patient tumors inevitably develop resistance to these drugs. This study will look at the effects of combining Vemurafenib, a drug that targets mutant BRAF proteins, and PX-866, a drug that targets the protein PI3K. Both mutant BRAF and PI3K are potent drivers of melanoma tumors, and the researchers believe that targeting both proteins at once may overwhelm the ability of the tumor to develop resistance.
2. Autophagy Modulation for Melanoma Therapy
Investigators: Ravit Amaravadi, M.D. (Penn) and David Speicher, Ph.D. (Wistar)
This project is designed to test the idea that inhibiting autophagy (cancer cells “eat themselves” in order to survive) will have a synergistic effect when used with BRAF inhibitors.
3. Association of Inherited Variation in Immune Mediated Adverse Events and Response to Ipilimumab
Investigators: Katherine Nathanson, M.D. (Penn) and Peter Kanetsky, Ph.D. (H. Lee Moffitt Cancer Center & Research Institute)
The goal of this project is to find the genetic markers that predict which patients do poorly when they take Ipilimumab, an FDA-approved drug that targets CTLA4, a protein that can slow the immune response to cancer. While the drug is designed to re-activate a patient’s immune system, in some patients it causes an over-reaction that is capable of causing death. By identifying genetic markers in over 1,000 patients from recent clinical trials, the researchers hope to identify which patients may be able to use Ipilimumab safely and effectively.
4. Engineered T Cell Therapy for Melanoma
Investigators: Robert Vonderheide, M.D., D.Phil., and Carl June, M.D. (Penn)
This project explores the use of “adoptive cellular therapy”—modifying a patient’s own T cells to target metastatic melanoma cells. The researchers will conduct a clinical trial that will take a patient’s T cell and transform them to target c-MET, a protein that cancer cells exhibit in overabundance on their surface.
In other news on melanoma research, a recent study established an alarming link between Viagra (sildenafil) and an increased risk for developing melanoma. According to the study entitled, “Sildenafil Use and Increased Risk of Incident Melanoma in US Men, A Prospective Cohort Study,” sildenafil can increase the invasiveness of melanoma cells.