The potential of retinoids for combination therapy of lung cancer: Updates and future directions

Lung cancer is the most common cancer-related death worldwide. Natural compounds have shown high biological and pharmaceutical relevance as anticancer agents. Retinoids are natural derivatives of vitamin A having many regulatory functions in the human body, including vision, cellular proliferation and differentiation, and activation of tumour suppressor genes. Retinoic acid (RA) is a highly active retinoid isoform with promising anti-lung cancer activity. The abnormal expression of retinoid receptors is associated with loss of anticancer activities and acquired resistance to RA in lung cancer. The preclinical promise has not translated to the general clinical utility of retinoids for lung cancer patients, especially those with a history of smoking. Newer retinoid nano-formulations and the combinatorial use of retinoids has been associated with lower toxicity and more favorably efficacy in both the preclinical and clinical settings. Here, we highlight epidemiological and clinical therapeutic studies involving retinoids and lung cancer. We also discuss the biological actions of retinoids in lung cancer, which include effects on cancer stem cell differentiation, angiogenesis, metastasis, and proliferative. We suggest that the use of retinoids in combination with conventional and targeted anticancer agents will broaden the utility of these potent anticancer compounds in the lung cancer clinic.