Heat shock proteins in thyroid malignancies: Potential therapeutic targets for poorly-differentiated and anaplastic tumours?

Mol Cell Endocrinol. 2020 Feb 15:502:110676. doi: 10.1016/j.mce.2019.110676. Epub 2019 Dec 6.

Abstract

Thyroid cancer is the most common endocrine malignancy, with well-differentiated subtypes characterized by an excellent prognosis due to their optimal sensitivity to standard therapies whereas poorly differentiated and anaplastic tumours by chemo/radio-resistance and unfavourable outcome. Heat Shock Proteins (HSPs) are molecular chaperones overexpressed in thyroid malignancies and involved in crucial functions responsible for thyroid carcinogenesis, as protection from apoptosis, drug resistance and cell migration. Thus, HSPs inhibitors have been proposed as novel therapeutic agents in thyroid cancer to revert molecular mechanisms of tumour progression. In this review, we report an overview on the biological role of HSPs, and specifically HSP90s, in thyroid cancer and their potential involvement as biomarkers. We discuss the rationale to evaluate HSPs inhibitors as innovative anticancer agents in specific subtypes of thyroid cancer characterized by poor response to therapies with the objective to target single family chaperones to reduce, simultaneously, the expression/stability of multiple client proteins.

Keywords: Chemoresistance; Drug target; Heat shock protein; Thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Drug Resistance, Neoplasm
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Molecular Targeted Therapy
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Heat-Shock Proteins