A pRB-depleted cell in mitosis.

The Engine of Discovery

Examples of key scientific discoveries made by CCR investigators that have substantially changed the way physicians understand and treat cancer include:

  • The identification of p53 gene mutations as the cause of the multi-cancer Li Fraumeni syndrome, leading to a widely used genetic test for individuals likely to have a predisposition to cancer (Science, 1990)
  • The discovery that genetic mutations in the Epidermal Growth Factor Receptor (EGFR) gene define a “non-smoker’s cancer” that is extremely responsive to a new class of targeted therapies (New England Journal of Medicine, 2004)
  • The finding that genetic alterations in the MET gene predict the response of gastric cancers to a new class of drugs (Proceedings of the National Academy of Sciences, 2005)
  • The design of specific genetic signatures that predict whether breast cancers are likely to respond to tamoxifen (Clinical Cancer Research, 2006) and to cisplatin (Journal of Clinical Investigation, 2007)
  • The isolation of a new gene responsible for many cases of Wilms tumor, a type of pediatric kidney cancer (Science, 2007)
  • The development of a microchip (using microfluidics technology) that is capable of purifying circulating tumor cells from the blood of patients with cancer, allowing noninvasive monitoring of cancer metastasis, and specifically making it possible to isolate “metastasis precursor cells” in lung and prostate cancers (Nature, 2007; New England Journal of Medicine, 2008)
  • The use of new RNA interference tools—capable of blocking specific gene products—to understand the process of "oncogene addiction" (a tumor cell’s dependence on one or just a few mutant genes to maintain the characteristics of a cancer cell) and to validate new therapeutic targets (Proceedings of the National Academy of Sciences, 2008)

Other CCR research discoveries, published in the most prestigious scientific and medical journals over just the past two years, will lead to future improvements in cancer diagnosis and therapy:

  • The finding that DNA damage-induced alterations in chromatin (the complex of DNA and histone proteins that make up our chromosomes) contribute to age-related changes in gene expression (Cell, 2008)
  • The discovery that a specific tumor suppressor pathway (p16/p19), which is frequently mutated in cancer, is down-regulated during the derivation of induced pluripotent stem (iPS) cells—iPS cells are a critical element of today’s stem cell research (Nature, 2009)
  • The ability to isolate and characterize circulating tumor cells in patients with localized and metastatic prostate cancer (Science Translational Medicine 2010)
  • The discovery of a link between cell metabolism and epigenetic programming (a form of gene regulation (Cell 2010)
  • The discovery of a chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations (Cell 2010)
  • The role of a specific gene in cancer metastasis regulation (Proceedings of the National Academy of Sciences USA 2010)

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