Genomic Approaches for Detection and Treatment of Breast Cancer
Final rept. 1 Jul 2004-30 Jun 2009
BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
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The experiments carried out under this Innovator award allowed us to set up a genetic system to identify genes through loss of function RNAi or gain of function over-expression functional screens that are capable of influencing cells to acquire tumorlike properties. In this way we have identified many novel tumor suppressors and oncogenes. Many of these are found to be altered in breast cancer and other cancer types. Importantly, we developed the ability to identify genes whose inhibition is lethal in cancer cells but not in normal cells. We discovered that many genes cancer cells depend on are not oncogenes but genes never implicated or altered in cancers. This introduced the concept of non-oncogene addiction and opened many researchers to the idea that there are many different potential anti-tumor drug targets that are only going to be found through functional screens for cancer cell vulnerabilities. In addition we devised and tested a novel peptide display technology using synthetic biology to probe the auto-immune response of cancer patients to look for early diagnosis biomarkers. We have synthesized the human peptidome and developed methodology to determine what portions of human proteins are being recognized by auto-anibodies on a genomic scale.
- Medicine and Medical Research