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Genome-specific synthetic lethal targeting in lung cancer

Institution: Stanford University
Investigator(s): Jonathan Pollack, M.D., Ph.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18XT-0158 Award: $400,000
Subject Area: Cancer
Award Type: Exploratory/Developmental Award

Initial Award Abstract
A very recent discovery is that about 15% of lung cancers contain amplification (i.e. extra copies) of the TITF1 gene, a transcription factor driving lung cancer development. Unique to lung cancer cells, TITF1 amplification would seem an ideal therapeutic target; however, targeting transcription factors has proven difficult. Our proposed studies are based on the concept of “synthetic lethality”, where cancer cells with specific genetic lesions (like TITF1 amplification) become particularly vulnerable in associated genes or pathways, providing an “Achilles heel” point of therapeutic attack. The goal of our proposed study is to discover those genes whose inactivation is lethal in combination with TITF1 amplification.

Our findings will improve our knowledge of the role of TITF1 amplification in lung cancer development, and will provide novel targets for the development of treatments for the 15% of lung cancers carrying TITF1 amplification. As such, the proposed research is directly responsive to TRDRP’s primary research priority of lung cancer.