Phase I Study of Epigenetic Priming with Azacitidine Prior to Standard Neoadjuvant Chemotherapy for Patients with Resectable Gastric and Esophageal Adenocarcinoma: Evidence of Tumor Hypomethylation as an Indicator of Major Histopathologic Response

• Published in: Clinical cancer research Vol. 23; no. 11; pp. 2673 - 2680
• Main Authors: Schneider, Bryan J., Shah, Manish A., Klute, Kelsey, Ocean, Allyson, Popa, Elizabeta, Altorki, Nasser, Lieberman, Michael, Schreiner, Andrew, Yantiss, Rhonda, Christos, Paul J., Palmer, Romae, You, Daoqi, Viale, Agnes, Kermani, Pouneh, Scandura, Joseph M.
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01.06.2017
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Azacitidine - administration & dosage; Bioindicators; Biomarkers; Bisulfite; Cancer; Chemotherapy; Cisplatin - administration & dosage; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Dose-Response Relationship, Drug; Epigenesis, Genetic - genetics; Epigenetics; Epirubicin; Epirubicin - administration & dosage; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophagus; Experimental design; Female; Fluorouracil - administration & dosage; Genes; Humans; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Patients; Priming; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Surgery; Toxicity; Tumor suppressor genes; Tumor Suppressor Proteins - drug effects; Tumor Suppressor Proteins - genetics

Purpose: Epigenetic silencing of tumor suppressor genes (TSG) is an acquired abnormality observed in cancer and is prototypically linked to DNA methylation. We postulated that pretreatment (priming) with 5-azacitidine would increase the efficacy of chemotherapy by reactivating TSGs. This study was c...