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.