Preprint Review Version 1 This version is not peer-reviewed

Chemotherapy-exacerbated Breast Cancer Metastasis: A Paradox Explainable by Stress Response

Version 1 : Received: 29 August 2018 / Approved: 29 August 2018 / Online: 29 August 2018 (09:05:46 CEST)

A peer-reviewed article of this Preprint also exists.

Middleton, J.D.; Stover, D.G.; Hai, T. Chemotherapy-Exacerbated Breast Cancer Metastasis: A Paradox Explainable by Dysregulated Adaptive-Response. Int. J. Mol. Sci. 2018, 19, 3333. Middleton, J.D.; Stover, D.G.; Hai, T. Chemotherapy-Exacerbated Breast Cancer Metastasis: A Paradox Explainable by Dysregulated Adaptive-Response. Int. J. Mol. Sci. 2018, 19, 3333.

Journal reference: Int. J. Mol. Sci. 2018, 19, 3333
DOI: 10.3390/ijms19113333

Abstract

An emerging picture in cancer biology is that, paradoxically, chemotherapy can actively induce changes that favor cancer progression. These pro-cancer changes can be either inside (intrinsic) or outside (extrinsic) the cancer cells. In this review, we will discuss the extrinsic pro-cancer effect of chemotherapy; that is, the effect of chemotherapy on the non-cancer host cells to promote cancer progression. We will focus on metastasis, and will first discuss recent data from mouse models of breast cancer. Intriguingly, despite reducing the size of primary tumors, chemotherapy changes the tumor microenvironment, resulting in an increased escape of cancer cells into the blood stream. Furthermore, chemotherapry changes the tissue microenvironment at the distant sites, making it more hospitable to cancer cells upon their arrival. We will then discuss the idea and evidence that these devastating pro-metastatic effects of chemotherapy can be explained in the context of stress response. At the end, we will discuss the potential relevance of these mouse data to human breast cancer and their implication on chemotherapy in the clinic.

Subject Areas

chemotherapy; breast cancer metastasis; stress response; ATF3; seed and soil theory; cancer-host interaction; tumor microenvironment; immune modulation; tumor immune environment

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