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Stem Cell Origin of Death-from-Cancer Phenotypes of Human Prostate and Breast Cancers

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Abstract

In clinical terms, all human cancers diagnosed in individuals can be divided in two major categories: malignant tumors that will be cured with the existing cancer therapies and tumors that have therapy-resistant phenotypes and will return after initial treatment as incurable metastatic disease. These tumors manifesting clinically lethal death-from-cancer phenotypes represent the most formidable challenge of experimental, translational, and clinical cancer research. Clinical genomics data demonstrate that gene expression signatures associated with the “stemness” state of a cell are informative as molecular predictors of cancer therapy outcome and can help to identify cancer patients with therapy-resistant tumors. Here, we present experimental and clinical evidence in support of the BMI1 pathway rule indicating a genetic link between the stemness state and therapy-resistant death-from-cancer phenotypes. Our analysis demonstrates that therapy-resistant and therapy-responsive cancer phenotypes manifest distinct patterns of association with stemness/differentiation pathways, suggesting that therapy-resistant and therapy-responsive tumors develop within genetically distinct stemness/differentiation programs. These differences can be exploited for development of prognostic and therapy selection genetic tests utilizing a microarray-based cancer therapy outcome predictor algorithm. One of the major regulatory pathways manifesting distinct patterns of association with therapy-resistant and therapy-responsive cancer phenotypes is the Polycomb group proteins chromatin silencing pathway.

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Acknowledgements

This work was supported in part by the grants from the Charitable Leadership Foundation (CLF, Clifton Park, New York), National Institute of Health, and Department of Defense.

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  1. Translational & Functional Genomics Laboratory, Ordway Cancer Center, Ordway Research Institute, Albany, NY, 12208, USA

    Gennadi V. Glinsky

  2. Department of Surgery, Division of Urology, and Department of Pathology & Laboratory Medicine, Albany Medical College, Albany, NY, 12208, USA

    Gennadi V. Glinsky

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Glinsky, G.V. Stem Cell Origin of Death-from-Cancer Phenotypes of Human Prostate and Breast Cancers. Stem Cell Rev 3, 79–93 (2007). https://doi.org/10.1007/s12015-007-0011-9

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