Working with the genome-wide cancer “dependency map” (inset below) Broad Institute researchers identified 760 genes that cancer cells need for their growth and survival.
In one of the largest efforts to build a comprehensive catalog of genetic vulnerabilities in cancer, researchers from the Broad Institute of MIT and Harvard and Dana-Farber Cancer Institute have identified more than 760 genes upon which multiple types of cancer cells are strongly dependent for their growth and survival.
Many of these “dependencies,” the researchers report today in the journal Cell, are specific to certain cancer types. However, about 10 percent of them are common across multiple cancers, suggesting that a relatively small number of therapies targeting these core dependencies might each hold promise for combating several tumors.
To generate these findings, the research team conducted genome-wide RNA interference (RNAi) screens on 501 cell lines representing more than 20 types of cancer, silencing more than 17,000 genes individually in each line to identify genetic dependencies unique to cancerous cells.
Cancer cells can harbor a broad variety of genetic errors, from small mutations to wholesale swaps of DNA between chromosomes. If an error shuts down a critical gene, a cancerous cell will compensate by adjusting other genes’ activity, frequently developing a dependence on such adaptations in order to persist.
Identifying these dependencies provides opportunities for scientists to gain deeper insight into cancer biology and determine new therapeutic targets.
“Much of what has been and continues to be done to characterize cancer has been based on genetics and sequencing. That’s given us the parts list,” said study co-senior author William Hahn, an institute member in the Broad Cancer Program, chief of the Division of Molecular and Cellular Oncology at Dana-Farber, and a leader in the Cancer Dependency Map initiative, a joint effort spanning the Broad Institute and Dana-Farber. “Mapping dependencies ascribes function to the parts and shows you how to reverse-engineer the processes that underlie cancer.”
RNAi silences genes using small pieces of RNA called small interfering RNAs (siRNAs). To run a genome-wide RNAi screen, researchers expose cells to pools of siRNAs and track the cells’ behavior.
“The simplest thing one can do with perturbed cells is allow them to keep growing over time and see which ones thrive,” explained study co-senior author David Root, an institute scientist and director of the Genetic…