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PI3K-AKT-mTOR Pathway Cooperates with the DNA Damage Repair Pathway: Carcinogenesis in Triple-Negative Breast Cancers and Beyond

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PI3K-mTOR in Cancer and Cancer Therapy

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

Abstract

Understanding of the biology of tumor cells of breast cancers like most of other solid tumors has undergone an evolutionary change at the molecular level with the advent of exome sequencing or whole genome sequencing technology. In today’s “clinic to laboratory and back” culture of medical practice, the genomics alteration-driven (biomarker) approach to cancer treatment has not only provided a better justification for the treatment of breast cancers but also added an invaluable tool for the diagnosis of “cancer evolution” and its therapeutic management. Recognizing the fact that the PI3K-mTOR pathway is a master regulator of tumor cell survival, proliferation, nutrient sensor, protein translation, metabolism, metastasis-associated phenotypes and angiogenesis, the PI3K pathway has been explored as one of the most studied targets in cancers. We here evaluated merits of the combination of DNA damage repair pathway inhibitor(s) with inhibitor(s) of the PI3K-mTOR pathway in targeting basal-like and triple-negative breast cancers. Sensitizing triple-negative breast cancer cells to inhibitors of DNA damage repair pathway by inhibitors of PI3K-mTOR pathway has been comprehensively discussed in the light of recent studies demonstrating that PI3K-AKT-mTOR pathway closely cooperates with the DNA damage repair pathway.

Review Criteria

The information for this chapter is compiled in part by searching the PubMed database for articles those are published before January 2016. Electronic early release publications listed in these databases are also included. Only articles published in English are considered. The search terms used included “Breast cancer” in association with the following search terms: “Apoptosis,” “proliferation,” “prognosis,” “cell signaling pathways,” “resistance,” “senescence,” “biomarkers,” “DNA Damage,” “DNA Damage Repair pathway,” “Triple-Negative Breast Cancer,” “HRD signature,” “PI3K-AKT-mTOR inhibitors,” “Basal-type Breast Cancer,” “PI3K-mTOR Pathway,” “chemotherapy,” “PARP inhibitor,” “BRCA1/BRCA2,” and “therapeutics.” These search terms are also used to search the abstracts from annual meetings and symposia.

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Acknowledgments

The authors also acknowledge Avera Cancer Institute Center for Precision Oncology, Sioux Falls, SD. The authors acknowledge the cBioPortal and STRING10. Cancer Discovery. May 2012 2; 401 (Cerami et al. [24] and Gao et al. [59]). We acknowledge the TCGA Research Network for generating TCGA datasets. We acknowledge the version 10 of STRING and authorities/institutions/organizations/Universities/resources which institutionally and financially support the STRING. The authors also acknowledge the Department of Internal Medicine, USD (Vermilion, SD). Authors acknowledge the secretarial help of Ms. Hannah Koble.

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Authors and Affiliations

  1. Avera Cancer Institute Center for Precision Oncology, Sioux Falls, SD, 57105, USA

    Pradip De, Jennifer H. Carlson, Brian Leyland-Jones & Nandini Dey

  2. Departmental of Internal Medicine, SSOM, University of South Dakota, Sioux Falls, SD, USA

    Pradip De, Brian Leyland-Jones & Nandini Dey

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  1. Oncology, Head of Cancer Biology, Avera Cancer Instit Center for Precision, SIOUX FALLS, South Dakota, USA

    Nandini Dey

  2. Oncology, Head of Translational Oncology, Avera Cancer Institute Center for Preci, Sioux Falls, South Dakota, USA

    Pradip De

  3. Precision Oncology,, Avera Cancer Institute Center for, Sioux Falls, South Dakota, USA

    Brian Leyland-Jones

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De, P., Carlson, J.H., Leyland-Jones, B., Dey, N. (2016). PI3K-AKT-mTOR Pathway Cooperates with the DNA Damage Repair Pathway: Carcinogenesis in Triple-Negative Breast Cancers and Beyond. In: Dey, N., De, P., Leyland-Jones, B. (eds) PI3K-mTOR in Cancer and Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-34211-5_3

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