TY - JOUR
T1 - Targeted therapy with kinase inhibitors in aggressive endocrine tumors
AU - Marotta, Vincenzo
AU - Franzese, Maria Domenica
AU - Del Prete, Michela
AU - Chiofalo, Maria Grazia
AU - Ramundo, Valeria
AU - Esposito, Raffaella
AU - Marciello, Francesca
AU - Pezzullo, Luciano
AU - Carratù, Annachiara
AU - Vitale, Mario
AU - Colao, Annamaria
AU - Faggiano, Antongiulio
PY - 2013/6
Y1 - 2013/6
N2 - Introduction: Kinase inhibitors (KIs) are a class of anticancer drugs that inhibit activity of the enzymes protein kinases, which regulate crucial cellular processes and have a demonstrated role in human oncogenesis. Treatment of advanced forms of endocrine cancer which are not responsive to cytotoxic chemotherapies is challenging and use of KIs is gaining a growing role in this field. Areas covered: The authors summarize the main genetic alterations known to be linked to endocrine tumors, indicating the rationale for utilizing KIs. Furthermore, they present an updated analysis of clinical trials available on PubMed Central, which were pertinent to the activities of KIs in aggressive endocrine cancer. The authors also discuss the adverse effects of KIs and summarize likely involved underlying mechanisms. Expert opinion: KIs are effective in obtaining a radiological disease control and an improvement of progression-free survival in several forms of endocrine cancer but will never deliver a knockout blow of the disease, due to mechanisms of adaptation to circumvent the specific molecular blockade. The new frontier of KIs treatment is to identify agents that could synergize activity of KIs. The true goal will be to perform an overall genotyping of each tumor, thus predicting the impact of combined targeted therapies in the context of a particular constellation of mutant genes.
AB - Introduction: Kinase inhibitors (KIs) are a class of anticancer drugs that inhibit activity of the enzymes protein kinases, which regulate crucial cellular processes and have a demonstrated role in human oncogenesis. Treatment of advanced forms of endocrine cancer which are not responsive to cytotoxic chemotherapies is challenging and use of KIs is gaining a growing role in this field. Areas covered: The authors summarize the main genetic alterations known to be linked to endocrine tumors, indicating the rationale for utilizing KIs. Furthermore, they present an updated analysis of clinical trials available on PubMed Central, which were pertinent to the activities of KIs in aggressive endocrine cancer. The authors also discuss the adverse effects of KIs and summarize likely involved underlying mechanisms. Expert opinion: KIs are effective in obtaining a radiological disease control and an improvement of progression-free survival in several forms of endocrine cancer but will never deliver a knockout blow of the disease, due to mechanisms of adaptation to circumvent the specific molecular blockade. The new frontier of KIs treatment is to identify agents that could synergize activity of KIs. The true goal will be to perform an overall genotyping of each tumor, thus predicting the impact of combined targeted therapies in the context of a particular constellation of mutant genes.
KW - Cancer therapy
KW - Endocrine tumors
KW - Kinase inhibitors
KW - Protein kinases
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UR - http://www.scopus.com/inward/citedby.url?scp=84877905276&partnerID=8YFLogxK
U2 - 10.1517/14656566.2013.796931
DO - 10.1517/14656566.2013.796931
M3 - Article
C2 - 23675883
AN - SCOPUS:84877905276
VL - 14
SP - 1187
EP - 1203
JO - Expert Opinion on Pharmacotherapy
JF - Expert Opinion on Pharmacotherapy
SN - 1465-6566
IS - 9
ER -