Breast cancer: origins and evolution

Journal of Clinical Investigation, Journal Year: 2007, Volume and Issue: 117(11), P. 3155 - 3163

Published: Nov. 1, 2007

Breast cancer is not a single disease, but rather composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity key for the development targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- intratumoral diversity are stem cell clonal evolution hypotheses. Although tumor initiation progression predominantly driven by acquired genetic alterations, recent data implicate role microenvironmental epigenetic changes as well. Comprehensive unbiased studies tumors patient populations have significantly advanced our molecular understanding breast cancer, translating these findings into practice remains challenge.

Language: Английский

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Clonal status of actionable driver events and the timing of mutational processes in cancer evolution

Science Translational Medicine, Journal Year: 2015, Volume and Issue: 7(283)

Published: April 15, 2015

Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types determine the subclonal frequencies events, time mutational processes during evolution, identify drivers expansions. Although known genes typically occurred early we also identified later "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), KRAS (G12D), which may compromise efficacy targeted therapy approaches. More than 20% glioblastomas, 15% PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target rapamycin) signaling axis across were subclonal. Mutations RAS-MEK (mitogen-activated protein kinase kinase) less associated with PI3K-AKT-mTOR signaling. Analysis late revealed link between APOBEC-mediated mutagenesis acquisition uncovered putative involved expansions, CTNNA2 ATXN1. Our results provide pan-cancer census events within context intratumor heterogeneity reveal patterns evolution cancers. The frequent presence suggests need stratify response according proportion is identified.

Language: Английский

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Metronomic chemotherapy: new rationale for new directions

Nature Reviews Clinical Oncology, Journal Year: 2010, Volume and Issue: 7(8), P. 455 - 465

Published: June 8, 2010

Language: Английский

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Co-evolution of tumor cells and their microenvironment

Trends in Genetics, Journal Year: 2008, Volume and Issue: 25(1), P. 30 - 38

Published: Dec. 5, 2008

Language: Английский

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Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity

Nature, Journal Year: 2014, Volume and Issue: 514(7520), P. 54 - 58

Published: July 29, 2014

Language: Английский

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