Tumor microenvironment and cancer therapy resistance.
Innate resistance to various therapeutic interventions is a hallmark of cancer. In recent years, however, acquired resistance has emerged as a daunting challenge to anticancer treatments including chemotherapy, radiation and targeted therapy, which abolishes the efficacy of otherwise successful regimens. Cancer cells gain resistance through a variety of mechanisms in both primary and metastatic sites, involving cell intrinsic and extrinsic factors, but the latter often remains overlooked. Mounting evidence suggests critical roles played by the tumor microenvironment (TME) in multiple aspects of cancer progression particularly therapeutic resistance. The TME decreases drug penetration, confers proliferative and antiapoptotic advantages to surviving cells, facilitates resistance without causing genetic mutations and epigenetic changes, collectively modifying disease modality and distorting clinical indices. Recent studies have set the baseline for future investigation on the intricate relationship between cancer resistance and the TME in pathological backgrounds. This review provides an updated outline of research advances in TME biology and highlights the prospect of targeting the TME as an essential strategy to overcome cancer resistance and improve therapeutic outcomes through precise intervention. In the long run, continued inputs into translational medicine remain highly desired to achieve durable responses in the current era of personalized clinical oncology.
Key Lab of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiaotong University School of Medicine, Shanghai 200031, China; Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiaotong University School of Medicine, Shanghai 200240, China; VA Seattle Medical Center, Seattle, WA 98108, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: sunyu@sibs.ac.cn.
Yu
Y
Sun
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D057285:Precision Medicine; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
Acquired resistance; Cancer therapy; Personalized medicine; Tumor microenvironment