Cancer cells can upregulate autophagy – recycling of components – as a response to chemotherapy. Investigators in Dr. Melvin DePamphilis’ laboratory at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) have shown that PIKFYVE inhibitors and p38 MAP kinase inhibitors work synergistically in vitro to kill cancer cells (e.g., colon adenocarcinomas, non-small cell lung carcinoma, glioblastoma, breast adenocarcinoma and osteosarcoma), but are not toxic to normal cells. Cancer cells with a BRAF mutation are especially dependent on autophagy. Treatment of cancer cells containing the BRAF mutation with PIKFYVE inhibitors can increase the efficacy of chemotherapy. Preliminary proof of concept in vivo studies indicate that the compounds work synergistically to inhibit tumor growth in a xenograft model.
NICHD seeks licenses and/or co-development partners for methods of treating cancer by administering PIKFYVE inhibitors and P38 MAP kinase inhibitors.
- Treatment of a wide range of cancers, including – but not limited to – colon adenocarcinomas, non-small cell lung carcinoma, glioblastoma, breast adenocarcinoma and osteosarcoma
- Cancers with BRAF mutations are common in primary markets such as the US, Europe, and Asia
- The methods of treating cancer by administering PIKFYVE and p38 MAP kinase inhibitors are selective for cancer cells and are not toxic to normal cells
- Potentially promising safety/toxicity profile for human use
Melvin DePamphilis (NICHD), Alex Vassilev (NICHD), Dina O'Connell (NICHD)
Sharma G, et al. A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis. [PMID 30806145]
- U.S. Provisional: U.S. Provisional Patent Application Number 62/927,966, Filed 30 Oct 2019
- PCT: PCT Application Number PCT/US2020/057655, Filed 28 Oct 2020