Cancer is a heterogeneous disease, with myriad distinct subtypes that differ in their genetic roots. As a result, cancers rely on varied pathways for survival--and respond differently to anticancer agents. The challenge for researchers is to precisely define those diverse pathways and pinpoint vulnerabilities that may serve as drug targets for new anti-cancer treatments. Investigators at the Whitehead Institute and the Broad Institute have taken an important step in tackling that challenge: They have succeeded in identifying the set of essential genes--those required for cellular proliferation and survival--in each of 14 human acute myeloid leukemia (AML) cell lines that had previously been characterized by genome sequencing. By combining their "gene essentiality map" with the existing genomic information, their study revealed liabilities in genetically defined subset of cancers that could be exploited for new therapies. The report on their work, appearing in the online edition of Cell on February 2, 2017, is entitled “Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.” A major aspect of the study focuses on the genes and protein pathways connected to the Ras oncogene, the most commonly mutated oncogene in human cancers which plays a role in AML, as well as many other cancers. "For the most part, the mutant Ras protein itself has been considered to be 'undruggable,’" explain Tim Wang, the paper's first author and an MIT graduate student researcher at Whitehead Institute and the Broad Institute. "An alternative approach has been to find other genes that Ras-mutant cancers rely on with the hope that one of them may be druggable.
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