BioCentury
ARTICLE | Distillery Therapeutics

Cancer

January 16, 2019 1:46 PM UTC

Cell culture and mouse studies suggest inhibiting PGD alone or in combination with OXPHOS complex I inhibition could help treat renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC), respectively. In a human hereditary leiomyomatosis RCC cell line, two PGD inhibitor tool compounds inhibited proliferation with EC50 values of 3 and 20 μM. Also in the cell line, two shRNAs targeting PGD decreased proliferation and increased markers of apoptosis compared with a non-targeting shRNA. In a xenograft mouse model of hereditary leiomyomatosis RCC, one of the PGD-targeting shRNAs decreased tumor volume. In three human NSCLC cell lines, the PGD-targeting shRNA plus IACS-010759, an inhibitor of OXPHOS complex I, decreased proliferation and increased markers of apoptosis compared with either agent alone. In a xenograft mouse model of NSCLC, the combination decreased tumor growth. Next steps include identifying and testing PGD inhibitors in animal models of hereditary leiomyomatosis RCC.

The University of Texas MD Anderson Cancer Center has IACS-010759 in Phase I testing for acute myelogenous leukemia (AML) and solid tumors...