How can doctors use immunotherapy to develop more effective and durable anticancer therapies? Is it possible to return aggressive cancer cells to a dormant form once they have spread? Those are two questions SKCC researchers Andrew Aplin, PhD, and Emad Alnemri, PhD, will explore with $1.3 million in grants from the Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee.
Aplin is Associate Director for Basic Research and Leader of the Cancer Cell Biology and Signaling Program at the Sidney Kimmel Cancer Center at Jefferson. In collaboration with Drs. Takami Sato, Jeffrey Benovic, Phil Wedegaertner and Julio Aguirre-Ghiso (Icahn School of Medicine at Mount Sinai), Aplin will receive $1 million to conduct a study on uveal melanoma, an aggressive form of eye cancer that is difficult to treat once it has spread. Uveal melanoma is characterized by metastasis to the liver; disseminated cells can remain dormant for years before suddenly awakening into an aggressive cancer. Aplin and his colleagues will study factors that direct metastasized cancer cells to remain dormant and those that cause the cancer to awaken. They will also examine whether it is possible to return growing uveal melanoma to a sleeping phase, where it would do less harm.
Aplin and his team will also explore more effective ways to understand the effect of mutations associated with disease initiation and strategies to combat uveal cancers that are actively growing in the liver. While they are dormant, the seeds of uveal melanoma are largely resistant to gene-targeted therapeutics, however, they could be susceptible to treatment when cancer is active.
Alnemri, Thomas Eakins Professor of Biochemistry and Molecular Biology at Thomas Jefferson University, will receive $300,000 to study cancer immunotherapy, which uses a patient’s own immune system as a weapon against cancer. Not all cancers are equally immunogenic — or recognizable to the immune system — so Alnemri and his colleagues will examine tumor recognition by the immune system with the goal of developing more effective and durable anticancer therapies.
When cancer cells begin to shrink or die in response to chemotherapy or radiation therapy, the cells emit signs of distress called damage-associated molecular patterns (DAMPs). The immune system picks up on these signs and initiates an attack of the remaining cells. But how and when cancer cells display these signals is not well understood, nor is it known whether it is possible to instigate the process. Alnemri and his colleagues recently discovered a molecular signal that induces DAMPs by helping the cell activate a protein that punches holes in the cellular membrane; this could be critical to initiating an immune-activating type of cell death. If proven accurate, the protein could be used to enhance or broaden the reach of existing anticancer therapies.
“Research is fundamental to enhance our understanding of cancer and help us develop better, more effective treatments,” Aplin said. “We are grateful to the Falk Trust for supporting our vital efforts aimed at improving therapies and finding cures for disease.”
The Dr. Ralph and Marian Falk Medical Research Trust Bank of America, N.A., Trustee, created by Marian Falk in 1979 to fund biomedical research, supports “medical research to improve treatments of the past and eventually find cures for diseases for which no definite cure is known.”
For more information, visit Jefferson.edu.