Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies
- 1 March 2009
- journal article
- review article
- Published by Bioscientifica in Endocrine-Related Cancer
- Vol. 16 (1), 17-44
- https://doi.org/10.1677/erc-08-0154
Abstract
Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy has improved locoregional control, the median survival of ∼ 4 months has not changed in more than half a century due to uncontrolled systemic metastases. The objective of this study was to review the literature in order to identify potential new strategies for treating this highly lethal cancer. PubMed searches were the principal source of articles reviewed. The molecular pathogenesis of ATC includes mutations in BRAF, RAS, catenin (cadherin-associated protein), beta 1, PIK3CA, TP53, AXIN1, PTEN, and APC genes, and chromosomal abnormalities are common. Several microarray studies have identified genes and pathways preferentially affected, and dysregulated microRNA profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, epigenetics, and protein degradation are affected. A variety of agents have been successful in controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With the recent increased knowledge of the many critical genes and proteins affected in ATC, and the extensive array of targeted therapies being developed for cancer patients, there are new opportunities to design clinical trials based upon tumor molecular profiling and preclinical studies of potentially synergistic combinatorial novel therapies.Keywords
This publication has 100 references indexed in Scilit:
- An Orthotopic Model of Anaplastic Thyroid Carcinoma in Athymic Nude MiceClinical Cancer Research, 2005
- Anaplastic thyroid carcinomaCancer, 2005
- Reduced E-cadherin expression contributes to the loss of p27 kip1 -mediated mechanism of contact inhibition in thyroid anaplastic carcinomasCarcinogenesis: Integrative Cancer Research, 2005
- Genome-Wide Profiling of Papillary Thyroid Cancer Identifies MUC1 as an Independent Prognostic MarkerCancer Research, 2004
- Anaplastic Thyroid Cancer: Cytogenetic Patterns by Comparative Genomic HybridizationThyroid®, 2003
- Combretastatin A4 Phosphate Has Primary Antineoplastic Activity Against Human Anaplastic Thyroid Carcinoma Cell Lines and Xenograft TumorsThyroid®, 2002
- BMP-7-Induced Cell Cycle Arrest of Anaplastic Thyroid Carcinoma Cells via p21CIP1 and p27KIP1Biochemical and Biophysical Research Communications, 2001
- Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP systemCancer Gene Therapy, 2001
- DNA Copy Number Changes in Thyroid CarcinomaThe American Journal of Pathology, 1999
- Treatment of anaplastic giant and spindle cell carcinoma of the thyroid gland with combination adriamycin and radiation therapy a new approachCancer, 1983