The role of chemotherapy and latest emerging target therapies in anaplastic thyroid cancer

Abstract

Anaplastic thyroid cancer represents 1%-2% of thyroid cancers. For its aggressiveness, it is considered a systemic disease at the time of diagnosis. Surgery remains the cornerstone of therapy in resectable tumor. Traditional chemotherapy has little effect on metastatic disease. A multimodality approach, incorporating cytoreductive surgical resection, chemoradiation, either concurrently or sequentially, and new promising target therapies is advisable. Doxorubicin is the most commonly used agent, with a response rate of 22%. Recently, other chemotherapy agents have been used, such as paclitaxel and gemcitabine, with superimposable activity and response rates of 10%-20%. However, survival of patients with anaplastic thyroid cancer has changed little in the past 50 years, despite more aggressive systemic and radiotherapies. Several new agents are currently under investigation. Some of them, such as sorafenib, imatinib, and axitinib have been tested in small clinical trials, showing promising disease control rates ranging from 35%-75%. Referral of patients for participation in clinical trials is needed.

Keywords: anaplastic thyroid carcinoma; chemotherapy; emerging therapies; radiotherapy; thyroid cancer.

Figure 1

The main route of tumor progression and dedifferentiation. Abbreviations: FA, follicular adenoma; FTC, follicular tumor cell; PTC, papillar thyroid carcinoma; FVPTC, follicular variant of papillary thyroid carcinoma; PDTC/ATC, poorly differentiated anaplastic tumor cancer; PPFP, paired box gene 8-peroxisome proliferator activated receptor; PI3K, phosphoinositide 3 kinase; RAS, rat sarcoma; RAF, rapidly accelerated fibrosarcoma; MEK, mitogen activated kinases; RET, rearranged during transfection; AKT, alpha serine/threonine-protein kinase.

Figure 2

Anaplastic thyroid cancer growth pathways. Note: The MAPK/ERK/PTEN pathway is a chain of proteins that communicates a proliferation signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Abbreviations: MAP, Mitogen-activated protein; ZO, zonula occludens; MAPK, MAP kinase; mTOR, mammalian target of rapamycin; ERK, extracellular signal-regulated kinase; PI3K, phosphoinositide 3 kinase; RET, rearranged during transfection; EGFR, epidermal growth factor receptor; RAS, rat sarcoma; RAF, rapidly accelerated fibrosarcoma; PIP, phosphatidylinositol phosphate; PTC, papillary thyroid cancer; AKT, alpha serine/threonine-protein kinase; PTEN, phosphatase and tensin homolog; P, phosphate; PCL, phospholipase C.