Chemoresistance and the tumor microenvironment - the critical role of cell-cell communication

Sep 21, 2026

Uploaded by Rowan

Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding how chemoresistance develops is essential for designing therapies that can counter it. Advances have increased attention to the tumor microenvironment (TME) and intercellular interactions, where multiple cell types communicate through cytokines, chemokines, growth factors, and extracellular vesicles (EVs), as well as direct contacts via gap junctions and cell adhesion. EV-mediated signaling and EV transport of drug-efflux components contribute to chemoresistance.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

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Abstract

Introduction

Wilczyński et al. Cell Communication and Signaling (2024) 22:486 [https://doi.org/10.1186/s12964-024-01857-7](https://doi.org/10.1186/s12964-024-01857-7) Cell Communication and Signaling REVIEW Open Access Chemoresistance and the tumor microenvironment: the critical role of cell–cell communication Bartosz Wilczyński 1, Alicja Dąbrowska 1, Julita Kul backa2,3* and Dagmara Baczyńska2 Abstract Resistance of cancer cells to anticancer drugs remains a major challenge in modern medicine. Understanding the mechanisms behind the development of chemoresistance is key to developing appropriate therapies to counteract it. Nowadays, with advances in technology, we are paying more and more attention to the role of the tumor microenvironment (TME) and intercellular interactions in this process. We also know that important elements of the TME are not only the tumor cells themselves but also other cell types, such as mesenchymal stem cells, cancer-associated fibroblasts, stromal cells, and macrophages. TME elements can communicate with each other indirectly (via cytokines, chemokines, growth factors, and extracellular vesicles [EVs]) and directly (via gap junctions, ligand–receptor pairs, cell adhesion, and tunnel nanotubes) . This communication appears to be critical for the development of chemoresistance. EVs seem to be particularly interesting structures in this regard. Within these structures, lipids, proteins, and nucleic acids can be transported, acting as signaling molecules that interact with numerous biochemical pathways, thereby contributing to chemoresistance. Moreover, drug efflux pumps, which are responsible for removing drugs from cancer cells, can also be transported via EVs. Keywords Chemoresistance, Cell–cell communication, Tumor microenvironment, Cancer Introduction The tumor microenvironment (TME), the cellular environment in which a tumor exists, consists of tumor cells, surrounding blood vessels, the extracellular matrix (ECM), and other non-malignant cells. However, the ECM also contains signaling molecules that facilitate cell-to-cell communication. It is a well-known fact that *Correspondence: Julita Kul backa [julita.kul backa@umw.edu.pl](julita.kul backa@umw.edu.pl) 1Faculty of Medicine, Wroclaw Medical University, Pasteura 1, Wroclaw 50-367, Poland 2Department of Molecular and Cellular Biology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, Wroclaw 50-556, Poland 3Department of Immunology and Bioelectrochemistry, State Research Institute Centre for Innovative Medicine, Santariškių g. 5, Vilnius LT-08406, Lithuania the TME includes not only stromal cells, fibroblasts, and immune cells (such as T lymphocytes, B lymphocytes, natural killer T cells, and tumor-associated macrophages [TAMs]) but also pericytes and sometimes adipocytes [1]. Interactions between cancer cells and other cells, as well as molecules released into the TME, play an important role in tumor growth and the suppression of antitumoral immunity [2]. Moreover, in response to evolving environmental conditions, the TME may change over the course of cancer progression, indicating its role in metastasis. It has been proven that stromal cells and fibroblastscan secrete numerous growth factors, such as CXCL12 chemokine, hepatocyte growth factor (HGF), and fibroblast growth factors (FGFs). These factors not only increase the growth and survival of tumor cells but also chemoattract other cells into the TME [3]. © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material der

FAQs

Why is chemoresistance a major challenge in cancer treatment?

Cancer cells resist anticancer drugs, making therapy outcomes difficult. The document emphasizes that clarifying the mechanisms of chemoresistance is key to developing effective counter-therapies.

What role does the tumor microenvironment (TME) play in chemoresistance?

The TME shapes chemoresistance through intercellular interactions. It includes multiple non-malignant cell types and signaling molecules that coordinate communication and support drug resistance.

How do extracellular vesicles (EVs) contribute to chemoresistance?

EVs transport lipids, proteins, and nucleic acids that act as signaling molecules across biochemical pathways. The document also notes that drug efflux pumps can be transported via EVs, helping remove drugs from cancer cells.

Sep 21, 2026

Uploaded by Rowan