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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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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