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Cancer Discov. 2014 Feb;4(2):146-8. doi: 10.1158/2159-8290.CD-13-1042.

Navigating the challenge of tumor heterogeneity in cancer therapy.

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1Cancer Therapeutics Program, Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne; 2Sir Peter MacCallum Department of Oncology and 3Department of Pathology, University of Melbourne, Parkville; and 4Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia.


The future of cancer treatment lies in personalized strategies designed to specifically target tumorigenic cell populations present in an individual. Although recent advances in directed therapies have greatly improved patient outcomes in some cancers, intuitive drug design is proving more difficult than expected owing largely to the complexity of human cancers. Intratumoral heterogeneity, the presence of multiple genotypically and/or phenotypically distinct cell subpopulations within a single tumor, is a likely cause of drug resistance. Advances in systems biology are helping to unravel the mysteries of cancer progression. In this issue of Cancer Discovery, Zhao and colleagues define a path for functional validation of computational modeling in the context of heterogeneous tumor populations and their potential for drug response and resistance.

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