Defining the susceptibility of colorectal cancers to BH3-mimetic compounds
- Luo, MJ; Palmieri, M; Riffkin, CD; Sakthianandeswaren, A; Djajawi, TM; Hirokawa, Y; Shuttleworth, V; Segal, DH; White, CA; Nhu, D; Lessene, G; Lee, M; Gibbs, P; Huang, DCS; Sieber, OM; Gong, JN;
Publication Year 2020-09-10, Volume 11, Issue #9, Page 735
- Journal Title
- Cell Death & Disease
- Publication Type
- Journal Article
- Novel targets are required to improve the outcomes for patients with colorectal cancers. In this regard, the selective inhibitor of the pro-survival protein BCL2, venetoclax, has proven highly effective in several hematological malignancies. In addition to BCL2, potent and highly selective small molecule inhibitors of its relatives, BCLxL and MCL1, are now available, prompting us to investigate the susceptibility of colorectal cancers to the inhibition of one or more of these pro-survival proteins. While targeting BCLxL, but not BCL2 or MCL1, on its own had some impact, most (15/17) of the immortalized colorectal cancer cell lines studied were efficiently killed by the combined targeting of BCLxL and MCL1. Importantly, these in vitro findings were confirmed in a xenograft model and, interestingly, in all (5/5) patient derived tumor organoids evaluated. Our results lend strong support to the notion that BCLxL and MCL1 are highly promising targets for further evaluation in efforts to improve the treatment of colorectal cancers.
- WEHI Research Division(s)
- Personalised Oncology; Blood Cells And Blood Cancer; Chemical Biology
- PubMed ID
- Publisher's Version
- Open Access at Publisher's Site
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2020-10-02 10:28:03Last Modified: 2020-10-02 10:38:10