Current Status and Perspectives Regarding the Therapeutic Potential of Targeting EGFR Pathway by Curcumin in Lung Cancer

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.