BioCentury
ARTICLE | Distillery Therapeutics

Cancer

November 14, 2017 10:58 PM UTC

Cell culture and mouse studies suggest Bcl-XL inhibitors could help treat glioma, prostate and other cancers harboring the IDH1 R123H mutation. In human glioma and prostate cancer cell lines, cells engineered to express the IDH1 R132H mutation were more sensitive to the Bcl-XL/BCL-2 inhibitor navitoclax than the corresponding cell lines expressing wild-type IDH1. Also in the cell lines, siRNA targeting Bcl-XL increased apoptosis of IDH1 R123H-mutant cells compared with a non-specific siRNA, whereas in the IDH1 wild-type cells, Bcl-XL knockdown had no effect. In the prostate cancer cell line, the BCL-2 inhibitor Venclexta venetoclax induced apoptosis in IDH1 R123H-mutant and wild-type cells with comparable potencies. In xenograft mouse models of glioma and prostate cancer, navitoclax decreased growth of tumors harboring the IDH1 mutation compared with vehicle, whereas in IDH1 wild-type tumors, the drug had no effect on tumor growth. Next steps could include testing Bcl-XL inhibitors in models of other cancers with the IDH1 mutation.

AbbVie Inc. has navitoclax (ABT-263) in Phase I/II testing for small cell lung cancer (SCLC) and other solid tumors and in preclinical testing for acute lymphoblastic leukemia (ALL)...