The role of tumor microenvironment in therapeutic resistance

Oncotarget. 2017 Jan 17;8(3):3933-3945. doi: 10.18632/oncotarget.13907.


Cancer cells undergo unlimited progression and survival owing to activation of oncogenes. However, support of the tumor microenvironment is essential to the formation of clinically relevant tumors. Recent evidence indicates that the tumor microenvironment is a critical regulator of immune escape, progression, and distant metastasis of cancer. Moreover, the tumor microenvironment is known to be involved in acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, occurrence of therapeutic resistance leads to reduced efficacy. This review highlights myeloid cells, cancer-associated fibroblasts, and mesenchymal stem cells consisting of the tumor microenvironment, as well as the relevant signaling pathways that eventually render cancer cells to be therapeutically resistant.

Keywords: cancer-associated fibroblasts; mesenchymal stem cells; myeloid cells; therapeutic resistance; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Drug Resistance, Neoplasm*
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Myeloid Cells / cytology
  • Myeloid Cells / metabolism
  • Neoplasms / metabolism*
  • Radiation Tolerance*
  • Tumor Microenvironment