title: PI3K/Akt/mTOR: A promising therapeutic target for non-medullary thyroid carcinoma.
abstract: Thyroid carcinoma (TC) is the most common endocrine malignancy. The pathogenesis of TC is complex and involves multiple genetic events that lead to activation of oncogenic pathways such as the MAP kinase (MAPK) pathway and the PI3K/Akt/mTOR pathway. The PI3K/Akt pathway has emerged as an important player in the pathogenesis of TC, particularly in follicular and advanced anaplastic or poorly differentiated TC. Because these patients have a poor prognosis, particularly when their tumors become resistant to the conventional treatment with radioactive iodine, efforts have been made to identify possible targets for therapy within these pathways. Orally available drugs targeting the PI3K/Akt/mTOR pathway are being used with success in treatment of several types of malignant tumors. There is an increasing amount of preclinical and clinical data supporting that this pathway may represent a promising target for systemic therapy in TC. The present review focuses on the most recent developments on the role of the PI3K/Akt pathway in the pathogenesis of non-medullary TC and will provide insight into how this pathway can be targeted either alone or in the context of multimodal therapeutic strategies for treatment of advanced TC.
authors.affiliation: Department of Endocrinology, University of Medicine and Pharmacy Cluj-Napoca Iuliu Hatieganu, 3-5 Louis Pasteur, 400349 Cluj-Napoca, Romania.
authors.forename: Mirela S
authors.initials: MS
authors.lastname: Petrulea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Smit
authors.affiliation: Department of Endocrinology, University of Medicine and Pharmacy Cluj-Napoca Iuliu Hatieganu, 3-5 Louis Pasteur, 400349 Cluj-Napoca, Romania.
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Georgescu
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands; Division of Endocrinology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.. Electronic address: Romana.Netea-Maier@radboudumc.nl.
authors.forename: Romana T
authors.initials: RT
authors.lastname: Netea-Maier
mesh_terms: D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D019468:Disease Management; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D014157:Transcription Factors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: Akt; PI3K; Therapy resistance; Thyroid carcinoma; Tumorigenesis; mTOR