Recent advances in precision medicine for the treatment of anaplastic thyroid cancer

Abstract

ABSTRACTIntroduction: Anaplastic thyroid cancer (ATC) is one of the most aggressive human malignancies (representing 15–40% of fatal TC cases), classified as stage IV by the American Joint Committee on Cancer, regardless of tumor size or presence of lymph node and distant metastases. A large number of genetic alterations are associated with ATC, especially causing dysfunctions in the ERK1/2-MEK1/2 and PI3K-AKT signaling pathways (BRAF, p53, RAS, EGFR, VEGFR1, VEGFR2, chromosomal rearrangements, etc). New drugs targeting these molecular pathways have recently been evaluated in ATC.Areas covered: This article reviews the recent advances in precision medicine for the treatment of ATC.Expert commentary: Interesting results have been reported with molecules targeting different pathways: 1) BRAF (dabrafenib/trametinib, vemurafenib); 2) angiogenesis (sorafenib, combretastatin, vandetanib, sunitinib, lenvatinib, CLM3, etc); 3) EGFR (gefitinib); 4) PPARγ agonists (rosiglitazone, pioglitazone, efatutazone).The potentiality of targeted drugs to synergize with radiation, chemotherapy, or other targeted drugs is currently under investigation to bypass resistance to a single drug. New affordable individual genomic analyses as well as the possibility to test these new treatments in primary cells from each ATC patient in vitro, could allow the personalization of the therapy, increasing the therapeutic effectiveness and avoiding the use of ineffective drugs.