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

ABSTRACT

Introduction: 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.

KEYWORDS:

• Anaplastic thyroid cancer
• molecular pathways
• targeted drugs
• precision medicine
• personalized therapy
• dabrafenib
• trametinib
• lenvatinib

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received honoraria from Bayer, Eisai, Aska and Sanofi, as well as receiving research funding from Bayer and Eisai. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded.