Neuroendocrine tumors. Molecular targeted therapy for carcinoid and islet-cell carcinoma.
Carcinoid and islet-cell carcinoma are often also known as low-grade neuroendocrine carcinomas. They are often slow-growing but can be resistant to standard therapy. While somatostatin analogues are often used to control hormonal syndromes, there is currently no therapy approved in the US for control of carcinoid tumor growth. For islet-cell carcinoma, streptozocin-based chemotherapy may induce tumor shrinkage, but second-line option are limited. This chapter reviews the molecular biology of neuroendocrine tumors, including the roles of MENIN, TSC2, NF-1, vHL, p53, bcl-2, bax, VEGF, IGF, PDGF, EGFR, and mTOR. Recently, there has been interest in developing molecularly targeted therapy for this group of diseases. Phase-II studies with imatinib, bevacizumab, sunitinib, gefitnib, temsirolimus, and everolimus (RAD001) have completed accrual. Encouraging results have been observed in studies with VEGF and mTOR inhibitors. Phase-III study of bevacizumab is planned in the US. Large-scale multinational phase-II and -III studies of everolimus are under way.
Yao
James C
JC
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. jyao@mail.mdanderson.org
D014408:Biomarkers, Tumor / Q000235:genetics; D018273:Carcinoma, Islet Cell / Q000235:genetics / Q000628:therapy*; D018390:Gene Targeting; D016313:Genes, abl; D018773:Genes, erbB-1; D015316:Genetic Therapy; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000628:therapy*; D010179:Pancreas / Q000098:blood supply; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D011494:Protein Kinases / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D058570:TOR Serine-Threonine Kinases
D014408:Biomarkers, Tumor; D011494:Protein Kinases; C546842:MTOR protein, human; D019009:Proto-Oncogene Proteins c-kit; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D017479:Receptors, Platelet-Derived Growth Factor; D058570:TOR Serine-Threonine Kinases