THE ROLE OF MULTIKINASE INHIBITORS IN THYROID CANCER THERAPY

Trusov Y. A., Berezovskaya K. I., Dautov A. S., KHismatullin R. R., Sufiyanova A. F., Salatov Ya. S., Kahramanov A. B., Muminov D. D.

BRAF V600E is the most common molecular change in prostate cancer, which is associated with tumor aggressiveness and an unfavorable prognosis due to the constant activation of the MAPK pathway leading to proliferation and survival of tumor cells. Therapy targeting key MAPK pathway proteins, such as RAF and MEK, has shown encouraging results in prostate cancer, but less impressive than in melanoma, where the MAPK pathway also underlies oncogenesis. Therefore, it is necessary to understand the differences in efficacy observed between thyroid cancer and other cancers with activation of the MAPK pathway, as well as the mechanisms of resistance to MAPKi. Drug resistance may arise due to genomic instability with the proliferation of previously existing resistant clones carrying internal mutations, or due to the emergence of new genetic and epigenetic changes that often activate the molecules of the MARK pathway. Several other resistance mechanisms have also been identified that induce paradoxical activation of the MARK pathway or recruitment of another proliferation signaling pathway.Therefore, there is a growing need for the development and research of new molecules targeting the MAPK pathway, such as pan-inhibitors of RAF, RAS or ERK inhibitors.

Keywords:Thyroid gland; thyroid cancer; MAPK inhibitors; targeted therapy; molecular biology; diagnostics