Markers involved in resistance to cytotoxics and targeted therapeutics in pancreatic cancer.
Pancreatic cancer retains a poor prognosis among the gastrointestinal cancers and remains a challenge in oncology. In 1997, gemcitabine became the standard of care in metastatic setting. In the last decades, despite a number of clinical trials assessing novel cytotoxic agents and cell signaling inhibitors, overall survival has reached a plateau that remains difficult to improve. Development of mechanisms implicated in intrinsic and acquired resistance to chemotherapy are considered to play a key role that could explain the limited benefit of most treatment in pancreatic cancers. Key molecular factors implicated in this process include: deficiencies in drugs uptake, activations of DNA repair pathways, resistance to apoptosis, and tumor microenvironment. Moreover, for cell signaling inhibitors, mutations in kinase domains, activation of alternative pathways, mutations of genes downstream of the target, activation of autocrine/paracrine pathways and/or feed-back amplification of the target represent the most important mechanisms achieving resistance of pancreatic cancer cells.
El Maalouf
Ghassan
G
Department of Medical Oncology, Service Inter-Hospitalier de Cancérologie Bichat-Beaujon, Beaujon University Hospital, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92118 Clichy Cedex, France. ghassan_maalouf@hotmail.com
Le Tourneau
Christophe
C
Batty
Georges Nicolas
GN
Faivre
Sandrine
S
Raymond
Eric
E
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor