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Combined PIKFYVE and p38 MAP Kinase Inhibition for Treating Cancer

Summary
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) seeks licenses and/or co-development partners for methods of treating cancer by administering PIKFYVE inhibitors and P38 MAP kinase inhibitors.
NIH Reference Number
E-138-2019
Product Type
Keywords
  • Oncology, Inhibition of Autophagy, PIKFYVE Inhibitors, p38 MAP Kinase Inhibitors, BRAF Mutation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD, Depamphilis
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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.

Potential Commercial Applications
  • 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
Competitive Advantages
  • 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
Inventor(s)

Melvin DePamphilis (NICHD), Alex Vassilev (NICHD), Dina O'Connell (NICHD)

Development Stage
Publications

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]

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 62/927,966, Filed 30 Oct 2019
Therapeutic Area
Updated
Monday, April 20, 2020