Project title: Treating NETs via synthetic lethality

General Description

Researchers will test an FDA approved inhibitor of MEK1/2 (FDA approved for melanoma) in preclinical models of neuroendocrine tumors. The results will provide insight into the unique mechanisms that drive neuroendocrine cancer growth. Positive results of an already approved drug could speed the path from the bench to the bedside to pave the way for clinical trials.

This project is based on the concept of “synthetic lethality.” This concept originated in genetics where synthetic lethality occurs between two genes when mutation of either alone is compatible with life but a mutation of both leads to death. Thus, targeting a synthetic lethal partner to a cancer-relevant mutation kills cancer cells and spares normal cells.

The results will provide insight into the unique mechanisms that drive neuroendocrine cancer growth; and with positive results from the preclinical studies, use of an FDA approved drug may provide rapid translation to patients with neuroendocrine cancers including pancreatic neuroendocrine cancer.

Publication

Chamberlain CE, German MS, Yang K, Wang J, VanBrocklin H, Regan M, Shokat KM, Ducker GS, Kim GE, Hann B, Donner DB, Warren RS, Venook AP, Bergsland EK, Lee D, Wang Y, Nakakura EK. A Patient-derived Xenograft Model of Pancreatic Neuroendocrine Tumors Identifies Sapanisertib as a Possible New Treatment for Everolimus-resistant Tumors. Mol Cancer Ther. 2018 Dec;17(12):2702-2709. doi: 10.1158/1535-7163.MCT-17-1204. Epub 2018 Sep 25.