Advances in pharmacotherapy for advanced thyroid cancer of follicular origin (PTC, FTC). New approved drugs and future therapies

Expert Opin Pharmacother. 2022 Apr;23(5):599-610. doi: 10.1080/14656566.2022.2030704. Epub 2022 Jan 21.

Abstract

Introduction: The most common altered signaling found in aggressive iodine-refractory thyroid cancers derived from follicular cells (RAI-TC) are RTK, MAPK, PI3K, WNT, BRAF, RAS, RET, and TP53. Tyrosine Kinase Inhibitors (TKI) are multi-kinase inhibitors able to act against different pathways, that elicit an anti-neoplastic activity.

Areas covered: The aim of this paper is to review recent novel molecular therapies of RAI-TC. Recently, sorafenib and lenvatinib, have been approved for the treatment of aggressive RAI-TC. Other studies are evaluating vandetanib and selumetinib in RAI-TC. Furthermore, preliminary studies have evaluated dabrafenib, and vemurafenib in BRAF mutated RAI-TC patients to re-induce 131-iodine uptake. The interplay between cells of the immune system and cancer cells can be altered by immune checkpoints inhibitors. The expression of PDL1 in RAI-TC was related to tumor recurrence and poor survival. Several clinical trials are investigating a combination of different therapies, such as lenvatinib and pembrolizumab.

Expert opinion: Mechanisms of resistance to TKIs inhibitors can be of intrinsic or acquired origin. An acquired resistance to lenvatinib, or sorafenib can be due to upregulation of FGFR; therefore, anti-FGFR agents are evaluated. A new strategy is to combine TKIs with immunotherapy. Several studies are evaluating lenvatinib and pembrolizumab in RAI-TC patients.

Keywords: Thyroid cancer; immune therapy; lenvatinib; sorafenib; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Phenylurea Compounds / therapeutic use
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Quinolines* / pharmacology
  • Quinolines* / therapeutic use
  • Signal Transduction
  • Sorafenib / therapeutic use
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Quinolines
  • Sorafenib