Therapeutic advances in anaplastic thyroid cancer: a current perspective

Abstract

Thyroid cancer incidence is increasing at an alarming rate, almost tripling every decade. In 2017, it was the fifth most common cancer in women. Although the majority of thyroid tumors are curable, about 2-3% of thyroid cancers are refractory to standard treatments. These undifferentiated, highly aggressive and mostly chemo-resistant tumors are phenotypically-termed anaplastic thyroid cancer (ATC). ATCs are resistant to standard therapies and are extremely difficult to manage. In this review, we provide the information related to current and recently emerged first-line systemic therapy (Dabrafenib and Trametinib) along with promising therapeutics which are in clinical trials and may be incorporated into clinical practice in the future. Different categories of promising therapeutics such as Aurora kinase inhibitors, multi-kinase inhibitors, epigenetic modulators, gene therapy using oncolytic viruses, apoptosis-inducing agents, and immunotherapy are reviewed. Combination treatment options that showed synergistic and antagonistic effects are also discussed. We highlight ongoing clinical trials in ATC and discuss how personalized medicine is crucial to design the second line of treatment. Besides using conventional combination therapy, embracing a personalized approach based on advanced genomics and proteomics assessment will be crucial to developing a tailored treatment plan to improve the chances of clinical success.

Keywords: Anaplastic thyroid Cancer; Clinical trial; Immunotherapy; Inhibitors; Therapeutics; Tumor.

Fig. 1

Current and promising therapeutics that can be employed for personalized medicine development: Clinically, ATC therapeutic regime involves use of more than one modality shown above (current therapies, depicted in grey color). Several promising categories of drugs were explored for their therapeutic implications and can be employed in single or combination with other drugs (depicted in green color). However, the best strategy would be to evaluate and design the personalized treatment plan by determining underlying mutations, genetic lesions, oncogenic signaling cascades and other metabolomic “Achilles heels”

Fig. 2

Different promising drugs/inhibitors that target several hallmarks of ATC including uncontrolled proliferation, resistance to apoptosis, immunosuppression, Epigenetic reprogramming, angiogenesis and metabolomic alterations