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PARP Inhibitors for Cancer Therapy pp 381–412Cite as

Synthetic Sickness with Molecularly Targeted Agents Against the EGFR Pathway

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D,volume 83))

Abstract

The discovery of novel synthetic sick and synthetic lethal interactions in tumors is paramount in the era of personalized medicine. Through these mechanisms, tumor cells may be preferentially killed while sparing healthy bystander tissue, thereby minimizing side effects. In this chapter, we will discuss in detail the nuances of synthetic sickness. Additionally, we will focus on one such potential induced synthetic sickness strategy involving the combined inhibition of the EGFR and PARP pathways. This concept revolves around the recent appreciation of several proteins within the EGFR pathway and their roles in DNA damage repair. We will discuss the mechanisms by which inhibition of the EGFR pathway induces a DNA repair deficiency, which is subsequently exploited by PARP inhibition. Clinical testing of these strategies is currently underway, and if successful, may impact the therapy of multiple tumor types.

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Acknowledgements

We would like to thank the Sidney Kimmel Foundation, the Breast Cancer Research Foundation of Alabama, Breast SPORE at UAB Career Development Award, AACR/Genentech, the Susan G. Komen Foundation, the Center for Clinical and Translational Science (CCTS), and the Medical Scientist Training Program (MSTP) at the University of Alabama in Birmingham for their support of some of the work mentioned in this chapter.

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Authors and Affiliations

  1. Department of Radiation Oncology, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, 35249, Birmingham, AL, USA

    Jennifer A. Stanley & Eddy S. Yang MD, PhD

  2. Comprehensive Cancer Center, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, 35249, Birmingham, AL, USA

    Jennifer A. Stanley & Eddy S. Yang MD, PhD

  3. Cell, Developmental and Integrative Biology, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, 35249, Birmingham, AL, USA

    Eddy S. Yang MD, PhD

  4. Pharmacology and Toxicology, University of Alabama at Birmingham School of Medicine, 176F HSROC Suite 2232B, 1700 6th Avenue South, 35249, Birmingham, AL, USA

    Eddy S. Yang MD, PhD

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  1. Jennifer A. Stanley
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  2. Eddy S. Yang MD, PhD
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Correspondence to Eddy S. Yang MD, PhD .

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Editors and Affiliations

  1. Northern Institute for Cancer Research and Newcastle University Institute for Ageing Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom

    Nicola J. Curtin

  2. CRUK-MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom

    Ricky A. Sharma

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Stanley, J., Yang, E. (2015). Synthetic Sickness with Molecularly Targeted Agents Against the EGFR Pathway. In: Curtin, N., Sharma, R. (eds) PARP Inhibitors for Cancer Therapy. Cancer Drug Discovery and Development, vol 83. Humana Press, Cham. https://doi.org/10.1007/978-3-319-14151-0_16

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