Targeting Master Regulators of the Breast Cancer Metastasis Transcriptome
Annual rept. 1 Jul 2013-30 Jun 2014
SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
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The goal of our work is to characterize and target the master regulators of the breast cancer metastasis transcriptome. We seek to elucidate the key factors controlling large scale genetic programs that bring about the metastasis phenotype and to discover ways to target these regulators. To this end, this year, we have made substantial progress. We have comprehensively completed transcriptome profiling of the largest set of breast cancer primarymetastasis matched pairs that we know of. We have characterized the gene expression programs and the corresponding master regulators of these programs. The first major program we have worked out is that of neoangiogenesis. We showed that our top regulators control metastasis vasculogenesis by controlling RECK, which in turn, orchestrates a highly coordinated neoangiogenic switch. We have also developed in vitro and genomic platforms that will enable us to work out the blueprint of the hierarchy of regulators controlling the metastasis gene program.
- Medicine and Medical Research