Abstract
Lung cancer has become the most prevalent cancer for the past three decades, and the 5-years survival rate of lung cancer is only ~20% nowadays. Chemotherapy is the mainstay of lung cancer therapy, especially for non-small cell lung cancer. However, drug resistance represents a principal cause of therapeutic failure in non-small cell lung cancer leading to therapeutic insensitivity, tumor recurrence, and disease progression. Indole hybrids have the potential to conquer drug resistance, enhance efficacy, reduce adverse events, and improve pharmacokinetic properties due to their capacity to inhibit multiple targets simultaneously. Moreover, indole hybrids osimertinib, mobocertinib, cediranib, and vizimpro are currently applied in clinics for lung cancer therapy, demonstrating that indole hybrids are valuable scaffolds in the treatment and eradication of lung cancer. This review provides a comprehensive overview of the evolving landscape of indole hybrids with the in vitro and in vivo efficacy against lung cancer, and the structure-activity relationships as well as mechanisms of action are also discussed, covering articles published from 2021 onward.