Nicotinic acetylcholine receptors in chemotherapeutic drugs resistance: An emerging targeting candidate

There is no definitive cure for cancer, and most of the current chemotherapy drugs have limited effects due to the development of drug resistance and toxicity at high doses. Therefore, there is an ongoing need for identifying the causes of chemotherapeutic resistance, and it will be possible to develop innovative treatment approaches based on these novel targeting candidates. Cigarette smoking is known to be one of the main causes of resistance to chemotherapeutic agents. Nicotine as a component of cigarette smoke is an exogenous activator of nicotinic acetylcholine receptors (nAChRs). It can inhibit apoptosis, increase cell proliferation and cell survival, reducing the cytotoxic effects of chemotherapy drugs and cause a reduced therapeutic response. Recent studies have demonstrated that nAChRs and their downstream signaling pathways have considerable implications in different cancer's initiation, progression, and chemoresistance. In some previous studies, nAChRs have been targeted to obtain better efficacies for chemotherapeutics. Besides, nAChRs-based therapies have been used in combination with chemotherapy drugs to reduce the side effects. This strategy requires lower doses of chemotherapy drugs compared to the conditions that must be used alone. Here, we discussed the experimental and clinical studies that show the nAChRs involvement in response to chemotherapy agents. Also, controversies relating to the effects of nAChR on chemotherapy-induced apoptosis are in our focus in this review article. Delineating the complex influences of nAChRs would be of great interest in establishing new effective chemotherapy regimens. [Display omitted]