Cancer cells are rife with mutations that should kill them. But they adapt, adjusting the activity of a variety of genes in ways that make up for the loss of the ones those mutations knock out. The cells come to depend on those genetic adjustments, creating new vulnerabilities that researchers could potentially exploit for treatment.
In this video, Jasper Neggers and Brenton Paolella of the Broad Institute's Cancer Dependency Map project discuss how upwards of one-third of all cancers may be vulnerable to treatments that attack one of two genes called VPS4A and VPS4B. The two are paralogs -- molecular fraternal twins, sharing similar structures and similar functions. Cancer cells that lose one become heavily dependent on the other. Neggers and Paolella's work suggests that treatments that target VPS4A could be effective against cancer cells lacking VPS4B, and vice versa.
Neggers JE, Paolella BR, et al. Synthetic lethal interaction between the ESCRT paralog enzymes VPS4A and VPS4B in cancers harboring loss of chromosome 18q or 16q. Cell Reports. Online December 15, 2020.