EGFR-Nrf2 pathway plays a role in cancer cell's chemoresistance

Abstract

Chemotherapy is the best method yet for the treatment of advanced cancers, but resistance to chemotherapy limits its therapeutic effect. This has prompted the development of many new approaches for the treatment of cancer. The most important and established is the epidermal growth factor receptor (EGFR) targeted therapy. Since alterations in the expression of gene and activity of the pathway may affect the sensitivity of cancer cells to conventional chemotherapy, it has evoked combination of EGFR targeted drugs and chemotherapy. In fact, EGFR targeted drugs have shown activity in combination with conventional antitumor treatments in preclinical and clinical trials. But there are a significant part of patients in clinical trials demonstrating an unfavourable response. Facing this dilemma, more research is needed to clarify the exact molecular mechanism of the interaction. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a key transcription factor for cell defense mechanisms that regulates the expression of electrophile and xenobiotic detoxification enzymes and drug efflux pump proteins. Moreover, Nrf2 can enhance resistance of cancer cells to chemotherapeutic drugs. And, it is clear that some upstream pathways of Nrf2 are the downstream of EGFR pathway. These significant conditions support the hypothesis that EGFR-Nrf2 pathway plays a role in cancer cell's chemoresistance. Attempts to confirm this hypothesis will provide new evidence in the treatment of combination of EGFR targeted drugs and chemotherapy and the development of new ways of combination of targeted therapy and chemotherapy.