Emerging Frontiers in the Treatment of Non-small Cell Lung Cancer: Innovations and Clinical Advances

Non-small cell lung cancer (NSCLC), which accounts for about 85% of lung cancer cases, remains a leading cause of cancer-related mortality worldwide. Over the past decade, the advent of immunotherapies, targeted agents, and molecularly guided strategies has transformed the therapeutic landscape. However, significant challenges persist: many patients still present with advanced disease, and uncertainties remain regarding treatment sequencing, integration of novel therapies, and management of cases without actionable mutations. This review highlights the evolving role of chemotherapy within the modern multimodal treatment paradigm of NSCLC and underscores its enduring relevance amidst rapid therapeutic innovation. While platinum-based chemotherapy has historically been the cornerstone of treatment, its role is now increasingly dynamic, serving as a critical component of combination regimens alongside immunotherapies and targeted approaches. Advances such as immune checkpoint inhibitors and therapies directed at oncogenic drivers like EGFR, ALK, and ROS1 have significantly improved patient outcomes, yet chemotherapy remains essential, particularly for patients without actionable mutations. Emerging strategies, including perioperative immunotherapy, antibody-drug conjugates, bispecific antibodies, and novel cytotoxic agents, promise to further enhance efficacy. In addition, molecular personalization and the use of circulating tumor DNA are opening new avenues for precision oncology.