Combination Strategies Involving Immune Checkpoint Inhibitors and Tyrosine Kinase or BRAF Inhibitors in Aggressive Thyroid Cancer

Int J Mol Sci. 2022 May 20;23(10):5731. doi: 10.3390/ijms23105731.


Thyroid cancer is the most common (~90%) type of endocrine-system tumor, accounting for 70% of the deaths from endocrine cancers. In the last years, the high-throughput genomics has been able to identify pathways/molecular targets involved in survival and tumor progression. Targeted therapy and immunotherapy individually have many limitations. Regarding the first one, although it greatly reduces the size of the cancer, clinical responses are generally transient and often lead to cancer relapse after initial treatment. For the second one, although it induces longer-lasting responses in cancer patients than targeted therapy, its response rate is lower. The individual limitations of these two different types of therapies can be overcome by combining them. Here, we discuss MAPK pathway inhibitors, i.e., BRAF and MEK inhibitors, combined with checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4. Several mutations make tumors resistant to treatments. Therefore, more studies are needed to investigate the patient's individual tumor mutation burden in order to overcome the problem of resistance to therapy and to develop new combination therapies.

Keywords: PD-1 inhibitors; PD-L1 inhibitors; immunotherapy; new checkpoint inhibitors; thyroid cancer; tyrosine kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Melanoma* / pathology
  • Neoplasm Recurrence, Local / drug therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins B-raf / metabolism
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / genetics


  • Immune Checkpoint Inhibitors
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Grants and funding

This research received no external funding.