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GSK3ß as a novel promising target to overcome chemoresistance in pancreatic cancer.
Pecoraro, Camilla; Faggion, Beatrice; Balboni, Beatrice; Carbone, Daniela; Peters, Godefridus J; Diana, Patrizia; Assaraf, Yehuda G; Giovannetti, Elisa.
Afiliação
  • Pecoraro C; Department of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV Amsterdam, the Netherlands; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.
  • Faggion B; Department of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV Amsterdam, the Netherlands.
  • Balboni B; Department of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV Amsterdam, the Netherlands; Computational and Chemical Biology, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy, and Department of Pharmacy and Biotechnology, University of Bologna, Via Bel
  • Carbone D; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.
  • Peters GJ; Department of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV Amsterdam, the Netherlands; Department of Biochemistry, Medical University of Gdansk, Poland.
  • Diana P; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Palermo, Italy.
  • Assaraf YG; The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
  • Giovannetti E; Department of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV Amsterdam, the Netherlands; Cancer Pharmacology Lab, Fondazione Pisana per la Scienza, Via Ferruccio Giovannini 13, 56017 San Giuliano Terme (Pisa), Italy. Electronic address: elisa.giovannetti@gmail.com.
Drug Resist Updat ; 58: 100779, 2021 09.
Article em En | MEDLINE | ID: mdl-34461526
Pancreatic cancer is an aggressive malignancy with increasing incidence and poor prognosis due to its late diagnosis and intrinsic chemoresistance. Most pancreatic cancer patients present with locally advanced or metastatic disease characterized by inherent resistance to chemotherapy. These features pose a series of therapeutic challenges and new targets are urgently needed. Glycogen synthase kinase 3 beta (GSK3ß) is a conserved serine/threonine kinase, which regulates key cellular processes including cell proliferation, DNA repair, cell cycle progression, signaling and metabolic pathways. GSK3ß is implicated in non-malignant and malignant diseases including inflammation, neurodegenerative diseases, diabetes and cancer. GSK3ß recently emerged among the key factors involved in the onset and progression of pancreatic cancer, as well as in the acquisition of chemoresistance. Intensive research has been conducted on key oncogenic functions of GSK3ß and its potential as a druggable target; currently developed GSK3ß inhibitors display promising results in preclinical models of distinct tumor types, including pancreatic cancer. Here, we review the latest findings about GSK-3ß biology and its role in the development and progression of pancreatic cancer. Moreover, we discuss therapeutic agents targeting GSK3ß that could be administered as monotherapy or in combination with other drugs to surmount chemoresistance. Several studies are also defining potential gene signatures to identify patients who might benefit from GSK3ß-based therapeutic intervention. This detailed overview emphasizes the urgent need of additional molecular studies on the impact of GSK3ß inhibition as well as structural analysis of novel compounds and omics studies of predictive biomarkers.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Resistencia a Medicamentos Antineoplásicos / Glicogênio Sintase Quinase 3 beta Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Resistencia a Medicamentos Antineoplásicos / Glicogênio Sintase Quinase 3 beta Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article