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A Study of Cancer Heterogeneity: From Genetic Instability to Epigenetic Diversity in Colorectal Cancer

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Abstract

Cancer is the leading cause of death worldwide. Despite improvements in diagnosis and treatment over the past two decades, cancer continues to present a serious challenge to oncologists, especially when the disease has already spread to a distant site at the time of diagnosis. The high degree of variation in gene expression, observed not only in tumors arising from different tissues but also in tumors arising from the same tissue, and sometimes in distinct areas of the same tumor, is likely to be responsible for evolutionary adaptation and consequently tumor survival.

Cellular heterogeneity has historically been viewed solely as the result of genetic instability. However, it has now become increasingly clear that changes in gene expression that occur without altering the DNA sequence—better known as epigenetic changes—can likewise contribute to tumorigenesis. Elucidating the mechanisms that account for cancer heterogeneity will be essential to the design of new drugs capable of overcoming the major limitations of current therapies. These limitations include the treatment of cancers able to escape immune surveillance or adapt to chemotherapy regimens as well as invasive and metastatic cancers.

Here, we review recent progress in the understanding of tumor genetics and epigenetics and translate these findings into potential clinical practice.

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Acknowledgements

This work was supported by Ri.MED foundation (M. G. F.) and NIH grant DK085711 (E. L.). The authors are grateful to Julie Chandler, Lynda Guzik, and Aaron DeWard for editorial assistance.

Author information

Authors and Affiliations

  1. Department of Pathology, McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Maria Giovanna Francipane Ph.D. & Eric Lagasse Pharm.D., Ph.D.

  2. Ri.MED Foundation, Palermo, Italy

    Maria Giovanna Francipane Ph.D.

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  1. Maria Giovanna Francipane Ph.D.
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  2. Eric Lagasse Pharm.D., Ph.D.
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Corresponding author

Correspondence to Eric Lagasse Pharm.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Pharmacutics & Pharmacutical Chemistry, University of Utah, Salt Lake City, Utah, USA

    You Han Bae

  2. Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom

    Randall J. Mrsny

  3. Department of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA

    Kinam Park

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Francipane, M.G., Lagasse, E. (2013). A Study of Cancer Heterogeneity: From Genetic Instability to Epigenetic Diversity in Colorectal Cancer. In: Bae, Y., Mrsny, R., Park, K. (eds) Cancer Targeted Drug Delivery. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7876-8_14

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