title: Current Status and Perspectives Regarding the Therapeutic Potential of Targeting EGFR Pathway by Curcumin in Lung Cancer.
abstract: Lung cancer is among the leading causes of cancer-related-death. Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. More than 70% of NSCLC patients have locally advanced or metastatic disease in diagnosis stage, which are then being treated with platinum-based chemotherapy or epidermal-growthfactor- receptor (EGFR) inhibitors. Several molecules which target multiple ErbB receptors and EGFR have been developed, including gefitinib and erlotinib. Identification of novel agents with less toxicity is warranted. Several interesting data have been reported about the antitumor activity of curcumin in several tumors, including lung, breast and colorectal cancers. In particular, a recent phase I trial evaluated the activity of curcumin in combination with FOLFOX chemotherapy in patients with inoperable colorectal cancer. They showed that curcumin added benefit in subsets of patients when administered with FOLFOX and was well-tolerated chemotherapy adjunct. Another ongoing trial is now investigating the beneficial effects of curcumin plus gefitinib or erlotinib for EGFRmutant NSCLC. Improved understanding of molecular mechanisms behind resistance to EGFR tyrosine kinase inhibitors suggests the importance of a genotype-guided approach to therapy and inhibition of parallel and downstream pathways, using agents which target heat-shock-protein-90, poly (ADP-ribose) polymerase and PI3K/mTOR pathway. The aim of the current review is to give an overview of the possible molecular mechanisms of curcumin in the preclinical and clinical investigations in solid tumors, with particular emphasis on its combination with other chemotherapeutic agents in lung cancers.
authors.affiliation: Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Shafiee
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Mohamadzade
authors.affiliation: Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Soudabeh
authors.initials: S
authors.lastname: ShahidSales
authors.affiliation: Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Khakpouri
authors.affiliation: Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Maftouh
authors.affiliation: Department of Biochemistry, Faculty of Science, Varastegan University, Mashhad. Iran.
authors.forename: Seyed Alireza
authors.initials: SA
authors.lastname: Parizadeh
authors.affiliation: Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Seyed Mahdi
authors.initials: SM
authors.lastname: Hasanian
authors.affiliation: Metabolic syndrome Research center, School of Medicine, Mashhad University of Medical Sciences, Mashhad. Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D003474:Curcumin
keywords: Curcumin; anticancer agents; clinical trial; in vivo models; lung cancer