The mechanistic role of curcumin and its analogs in NSCLC: An evaluation of cell death in preclinical studies

Abstract Lung cancer is the leading malignancy among males and ranks the second in females, with an estimated two million new diagnoses annually. It ranks the first in cancer‐related deaths among men and the second, following breast cancer, among women. The most significant risk factor for lung cancer is smoking. There are two main types of lung cancer: non‐small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with about 85% of cases falling into the NSCLC category. Even with a combination of treatments for NSCLC, such as surgical intervention, chemotherapy, radiation therapy, and immunotherapy, the 5‐year survival rates for those diagnosed with advanced NSCLC have not reached satisfactory levels, with chemotherapy continuing to be the main therapeutic approach. In advanced NSCLC treatment, gemcitabine and platinum‐based agents are applied as first‐line therapy. However, acquired or pre‐existing drug resistance can prevent chemotherapeutic agents from achieving the expected effect on patients and increasing the drug dose can lead to an increase in side effects. In recent years, for these reasons, there has been an increased interest in phytochemicals to enhance the cytotoxic effects of therapeutic agents on cancer cells while minimizing their toxic effects on healthy tissues. One of the most studied phytochemicals is curcumin. Despite its anticancer effects on NSCLC cells, its low stability and poor pharmacokinetics have led to unsatisfactory results in studies. Therefore, a variety of analogs have been synthesized. This review explores the impact of curcumin and its analogs on the pathways of cell death in NSCLC.