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.

The TUSC2 Tumour Suppressor Inhibits the Malignant Phenotype of Human Thyroid Cancer Cells via SMAC/DIABLO Protein

“…Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers; it can be derived from normal thyroid follicular cells (thyrocytes) or directly from well-differentiated thyroid cancer. ATC cases are generally incurable as they present a high rate of distant metastasis leading to death in less than one year from diagnosis; fortunately, the percentage of ATC cases is very low [15,21,22]. .…”

“…Undifferentiated or anaplastic thyroid cancer (ATC) is one of the most aggressive human tumours refractory to standard treatments with a very poor prognosis. ATC patients usually present a rapidly enlarging neck mass, a high rate of distant metastases and approximately 95% mortality at six months [15,16]. Conversely, well-differentiated papillary thyroid carcinoma (PTC), the most common type of thyroid cancer [17], is characterized by a good outcome as it is highly curable by surgery and radioiodine therapy; nevertheless some PTC patients have an aggressive disease and can develop distant metastasis [18].…”

TRIM11 promotes the proliferation, migration and chemoresistance of anaplastic thyroid cancer by stabilizing YAP

“…Well differentiated thyroid cancer is the most common thyroid cancer, accounting for approximately 90% of all cases. It is one of the most indolent tumors, which exhibits excellent prognosis with > 98% 5-year survival [4][5][6]. Anaplastic thyroid cancer is a small subset of thyroid cancer.…”

Effective Lenvatinib Treatment Complicated with Secondary Tracheocutaneous Fistula in Patients with Advanced Anaplastic Thyroid Carcinoma

“…Anaplastic thyroid carcinoma (ATC) accounts for only 1-2% of thyroid cancer but contributes to more than 50% of thyroid cancer-related mortalities [1]. Patients with ATC have a poor prognosis, with a median survival of 5-6 months [2,3].…”

“…Patients with ATC have a poor prognosis, with a median survival of 5-6 months [2,3]. Treatment outcome of ATC is often unsatisfactory by conventional chemotherapeutics or even combined multi-modality treatments [1,4].…”