Samuel A Wells1, Massimo Santoro. 1. Cancer Genetics Branch (S.A.W.), National Cancer Institute, Bethesda, Maryland 20892; and Dipartimento di Medicina Molecolare e Biotecnologie Mediche (M.S.), Universita' di Napoli "Federico II," 80131 Napoli, Italy.
Abstract
CONTEXT: Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. OBJECTIVE: This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. RESULTS: PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. CONCLUSIONS: A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.
CONTEXT: Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. OBJECTIVE: This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. RESULTS: PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. CONCLUSIONS: A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: David S Hong; Maria E Cabanillas; Jennifer Wheler; Aung Naing; Apostolia M Tsimberidou; Lei Ye; Naifa L Busaidy; Steven G Waguespack; Mike Hernandez; Adel K El Naggar; Alder K El Naggar; Savita Bidyasar; John Wright; Steven I Sherman; Razelle Kurzrock Journal: J Clin Endocrinol Metab Date: 2011-02-02 Impact factor: 5.958
Authors: J Robbins; M J Merino; J D Boice; E Ron; K B Ain; H R Alexander; J A Norton; J Reynolds Journal: Ann Intern Med Date: 1991-07-15 Impact factor: 25.391
Authors: Keith C Bible; Vera J Suman; Julian R Molina; Robert C Smallridge; William J Maples; Michael E Menefee; Joseph Rubin; Kostandinos Sideras; John C Morris; Bryan McIver; Jill K Burton; Kevin P Webster; Carolyn Bieber; Anne M Traynor; Patrick J Flynn; Boon Cher Goh; Hui Tang; Susan Percy Ivy; Charles Erlichman Journal: Lancet Oncol Date: 2010-09-17 Impact factor: 41.316
Authors: Cory M Johannessen; Jesse S Boehm; So Young Kim; Sapana R Thomas; Leslie Wardwell; Laura A Johnson; Caroline M Emery; Nicolas Stransky; Alexandria P Cogdill; Jordi Barretina; Giordano Caponigro; Haley Hieronymus; Ryan R Murray; Kourosh Salehi-Ashtiani; David E Hill; Marc Vidal; Jean J Zhao; Xiaoping Yang; Ozan Alkan; Sungjoon Kim; Jennifer L Harris; Christopher J Wilson; Vic E Myer; Peter M Finan; David E Root; Thomas M Roberts; Todd Golub; Keith T Flaherty; Reinhard Dummer; Barbara L Weber; William R Sellers; Robert Schlegel; Jennifer A Wargo; William C Hahn; Levi A Garraway Journal: Nature Date: 2010-11-24 Impact factor: 49.962
Authors: Poulikos I Poulikakos; Yogindra Persaud; Manickam Janakiraman; Xiangju Kong; Charles Ng; Gatien Moriceau; Hubing Shi; Mohammad Atefi; Bjoern Titz; May Tal Gabay; Maayan Salton; Kimberly B Dahlman; Madhavi Tadi; Jennifer A Wargo; Keith T Flaherty; Mark C Kelley; Tom Misteli; Paul B Chapman; Jeffrey A Sosman; Thomas G Graeber; Antoni Ribas; Roger S Lo; Neal Rosen; David B Solit Journal: Nature Date: 2011-11-23 Impact factor: 49.962
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