Cellular plasticity and drug resistance in sarcoma

Life Sci. 2020 Dec 15:263:118589. doi: 10.1016/j.lfs.2020.118589. Epub 2020 Oct 15.

Abstract

Sarcomas, originating from mesenchymal progenitor stem cells, are a group of rare malignant tumors with poor prognosis. Wide surgical resection, chemotherapy, and radiotherapy are the most common sarcoma treatments. However, sarcomas' response rates to chemotherapy are quite low and sarcoma cells can have intrinsic or acquired resistance after treatment with chemotherapeutics drugs, leading to the development of multi-drug resistance (MDR). Cancer cellular plasticity plays pivotal roles in cancer initiation, progression, therapy resistance and cancer relapse. Moreover, cancer cellular plasticity can be regulated by a multitude of factors, such as genetic and epigenetic alterations, tumor microenvironment (TME) or selective pressure imposed by treatment. Recent studies have demonstrated that cellular plasticity is involved in sarcoma progression and chemoresistance. It's essential to understand the molecular mechanisms of cellular plasticity as well as its roles in sarcoma progression and drug resistance. Therefore, this review focuses on the regulatory mechanisms and pathological roles of these diverse cellular plasticity programs in sarcoma. Additionally, we propose cellular plasticity as novel therapeutic targets to reduce sarcoma drug resistance.

Keywords: Cellular plasticity; Drug resistance; Epithelial-mesenchymal transition; Sarcoma; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Plasticity / physiology*
  • Disease Progression
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Humans
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents