Daniel M Girardi1, Andrea C B Silva2, Juliana Florinda M Rêgo3, Renata A Coudry4, Rachel P Riechelmann5. 1. Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil. Electronic address: danielmgirardi@gmail.com. 2. Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil. Electronic address: andreacbs87@gmail.com. 3. Unit of Oncology and Hematology, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte, Rio Grande do Norte, Brazil. Electronic address: juliana.oncologia@gmail.com. 4. Oncology Center, Hospital Sírio Libanês, São Paulo, Brazil. Electronic address: renata.coudry@gmail.com. 5. Discipline of Radiology and Oncology, Instituto do Câncer do Estado de São Paulo, Universidade de São Paulo, São Paulo, Brazil; Oncology Center, Hospital Sírio Libanês, São Paulo, Brazil. Electronic address: rachelri2005@gmail.com.
Abstract
BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive tumors. Their molecular pathogenesis is still largely unknown, and consequently, the best therapeutic management also remains to be determined. We conducted a systematic review on molecular alterations found in gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of targeted therapies in setting. MATERIALS AND METHODS: Systematic review of studies about molecular features in tumor tissues of patients with GEP-NECs. The Medline, Lilacs, Embase, Cochrane, Scopus and Opengrey databases were sought, without time, study design or language restrictions. RESULTS: Of the 1.564 studies retrieved, 41 were eligible: 33 were retrospective studies and eight were case reports. The studies spanned the years 1997-2017 and involved mostly colorectal, stomach and pancreas primary tumors. Molecular alterations in the TP53 gene and the p53 protein expression were the most commonly observed, regardless of the primary site. Other consistently found molecular alterations were microsatellite instability (MSI) in approximately 10% of gastric and colorectal NEC, and altered signaling cascades of p16/Rb/cyclin D1, Hedgehog and Notch pathways, and somatic mutations in KRAS, BRAF, RB1 and Bcl2. In studies of mixed adeno-neuroendocrine carcinomas (MANECs) the molecular features of GEP-NEC largely resemble their carcinoma/adenocarcinomas tumor counterparts. CONCLUSIONS: Despite the paucity of data about the molecular drivers associated with GEP-NEC, some alterations may be potentially targeted with new cancer-directed therapies. Collaborative clinical trials for patients with advanced GEP-NEC are urgently needed.
BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive tumors. Their molecular pathogenesis is still largely unknown, and consequently, the best therapeutic management also remains to be determined. We conducted a systematic review on molecular alterations found in gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of targeted therapies in setting. MATERIALS AND METHODS: Systematic review of studies about molecular features in tumor tissues of patients with GEP-NECs. The Medline, Lilacs, Embase, Cochrane, Scopus and Opengrey databases were sought, without time, study design or language restrictions. RESULTS: Of the 1.564 studies retrieved, 41 were eligible: 33 were retrospective studies and eight were case reports. The studies spanned the years 1997-2017 and involved mostly colorectal, stomach and pancreas primary tumors. Molecular alterations in the TP53 gene and the p53 protein expression were the most commonly observed, regardless of the primary site. Other consistently found molecular alterations were microsatellite instability (MSI) in approximately 10% of gastric and colorectal NEC, and altered signaling cascades of p16/Rb/cyclin D1, Hedgehog and Notch pathways, and somatic mutations in KRAS, BRAF, RB1 and Bcl2. In studies of mixed adeno-neuroendocrine carcinomas (MANECs) the molecular features of GEP-NEC largely resemble their carcinoma/adenocarcinomas tumor counterparts. CONCLUSIONS: Despite the paucity of data about the molecular drivers associated with GEP-NEC, some alterations may be potentially targeted with new cancer-directed therapies. Collaborative clinical trials for patients with advanced GEP-NEC are urgently needed.
Authors: Melissa Frizziero; Elaine Kilgour; Kathryn L Simpson; Dominic G Rothwell; David A Moore; Kristopher K Frese; Melanie Galvin; Angela Lamarca; Richard A Hubner; Juan W Valle; Mairéad G McNamara; Caroline Dive Journal: Clin Cancer Res Date: 2022-05-13 Impact factor: 13.801
Authors: Alberto Puccini; Kelsey Poorman; Mohamed E Salem; Davide Soldato; Andreas Seeber; Richard M Goldberg; Anthony F Shields; Joanne Xiu; Francesca Battaglin; Martin D Berger; Ryuma Tokunaga; Madiha Naseem; Afsaneh Barzi; Syma Iqbal; Wu Zhang; Shivani Soni; Jimmy J Hwang; Philip A Philip; Stefania Sciallero; W Michael Korn; John L Marshall; Heinz-Josef Lenz Journal: Clin Cancer Res Date: 2020-09-03 Impact factor: 12.531
Authors: Victor Hugo Fonseca de Jesus; Tiago Cordeiro Felismino; Milton José de Barros E Silva; Virgílio de Souza E Silva; Rachel P Riechelmann Journal: Clinics (Sao Paulo) Date: 2018-10-18 Impact factor: 2.365