Abstract
Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.
Highlights
Cancer is a multifactorial disease and is one of the leading causes of death worldwide
We evaluated the effect of esophageal WHCO1 and breast MDA MB 231 cancer cells on Wharton’s Jelly-derived mesenchymal stromal/stem cells (WJ-Mesenchymal Stromal/Stem Cells (MSCs)) gene expression over 24 days of co-culture
We observed that Smad2 increased in WJ-MSCs cocultured with WHCO1 and MDA MB 231 cells. These results demonstrate that the transforming growth factor-β (TGF-β)/Smad signaling pathway is involved in the differentiation of MSCs into tumor associated fibroblasts (TAFs) and that TGF-β probably is probably produced by both MSCs and cancer cells
Summary
Cancer is a multifactorial disease and is one of the leading causes of death worldwide. Despite the development of potent chemotherapeutics against many cancer types in recent years, durable or long lasting cure is still out of reach for many patients [3,4] This is partly due to the development of drug/therapeutic resistance which stems from the remarkable adaptive behavior of cancer cells and is driven by both genetic and epigenetic factors. Most important is the diversity within the tumor microenvironment (TM) in terms of the stromal cells present, the amount of oxygen available and the acidity of the environment [18,19,20,21,22,23,24] Another important difference is the amount of the extracellular matrix (ECM) proteins around the cancer cells [25,26,27]. Sci. 2017, 18, 1586 agents to reach cancer cells near the center of the tumor All these factors can have a huge influence on how cancer cells respond to drugs. It is imperative that the TM contribution be studied and specified as only can we attain long lasting treatment in clinical oncology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
