Milestones in Cancer Research

The Center for Cancer Research (CCR) researchers' diverse studies using cell culture, fruit flies, mouse models, human tumor samples, computational modeling, and advanced microfluidic and robotic systems bring new promises of effective therapies and prevention for all types of human cancer.

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)
• 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)
• The first engineered microfluidic “Chip” to isolate Circulating Tumor Cells (CTCs) from the blood of patients with cancer (Nagrath et al., Nature 2007) and the role of CTC-Clusters in metastasis (Aceto et al., Cell 2014)
• High throughput screening of a thousand cancer cell lines to uncover drug susceptibility patterns (Garnett et al., Nature 2012), with the first description of “persister cancer cells” that precede the emergence of drug resistance (Sharma et al., Cell 2012) and high throughput patient-derived cultures to predict drug resistance mechanisms (Crystal et al., Science 2014)
• Dissection of chromatin deregulation underlying pediatric Ewings Sarcoma (Boulay et al., Cell 2017) and colorectal cancer (Johnstone et al., Cell 2020)
• Genome-wide analyses of non-coding cancer drivers (Rheinbay et al., Nature 2020)
• Single cell resolution molecular analyses to dissect the diverse origins of brain cancers (Neftel et al., Cell 2019) and the discovery of immune cell “hubs” within cancers, linked to immunotherapy response (Pelka et al., Cell 2021)

These and many other publications point to the exceptional quality, the diverse breadth and the major impact of research discoveries from CCR investigators.

Learn more in our 2022 annual report (pdf)