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Tumor microenvironment promotes breast cancer chemoresistance

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Abstract

Breast cancer is presently the most predominant tumor type and the second leading cause of tumor-related deaths among women. Although advancements in diagnosis and therapeutics have momentously improved, chemoresistance remains an important challenge. Tumors oppose chemotherapeutic agents through a variety of mechanisms, with studies revealing that the tumor microenvironment (TME) is central to this process. The components of TME including stromal cells, immune cells, and non-stromal factors on exposure to chemotherapy promote the acquisition of resistant phenotype. Consequently, limited targeting of tumor cells leads to tumor recurrence after chemotherapy. Here, in this article, we summarize how TME alters chemotherapy responses in breast cancer. Furthermore, the role of different stromal cells viz., CAFs, TAMs, MSCs, endothelial cells, and cancer stem cells (CSC) in breast cancer chemoresistance is discussed in greater detail.

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Abbreviations

bFGF:

Basic fibroblast growth factor

CAF:

Cancer associated fibroblast

CCL:

Chemokine (C–C motif) ligand

CCR:

Chemokine (C–C motif) receptor

CSF:

Colony-stimulating factor

ECM:

Extracellular matrix

JNKs:

C-Jun N-terminal kinases

NF-κB:

Nuclear factor κB

STAT:

Signal transduction and transcription

SPP1:

Secreted phosphoprotein 1

TAMs:

Tumor-associated macrophages

TGF-β:

Transforming growing factor-β

TNC:

Tenascin C

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors are thankful to the University Grants Commission (UGC) Govt. of India, New Delhi, and the University of Kashmir, Srinagar J&K for their support. Umar Mehraj is a recipient of the junior research fellowship (JRF) from UGC-CSIR, India.

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Authors and Affiliations

  1. Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, 190006, J&K, India

    Umar Mehraj & Manzoor A. Mir

  2. Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal, J&K, 191201, India

    Abid Hamid Dar & Nissar A. Wani

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  1. Umar Mehraj
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  2. Abid Hamid Dar
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  3. Nissar A. Wani
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MAM initiated the study, designed the plan, and edited the manuscript. MAM, UM and NAW wrote the manuscript and designed the figures and tables. MAM, NW, AHD, and UM reviewed the manuscript and arranged the references. MAM, AHD, NW, and UM read and approved the final manuscript.

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Correspondence to Manzoor A. Mir.

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Mehraj, U., Dar, A.H., Wani, N.A. et al. Tumor microenvironment promotes breast cancer chemoresistance. Cancer Chemother Pharmacol 87, 147–158 (2021). https://doi.org/10.1007/s00280-020-04222-w

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