Intratumoral Therapeutic Injections for Lung Cancer: Current Evidence, Personalized Therapeutic Approaches, and Future Directions

Lung cancer remains the leading cause of cancer-related mortality worldwide despite significant advances in surgery, radiation therapy, targeted therapies, and immunotherapy. Although systemic therapies have improved outcomes across all stages of disease, treatment efficacy is often limited by inadequate intratumoral drug delivery, systemic toxicities, treatment resistance, and disease heterogeneity. Intratumoral therapeutic injections (ITIs), including intratumoral chemotherapy (ITC), have emerged as a promising locoregional therapeutic strategy designed to overcome these limitations through direct delivery of antineoplastic agents into tumor tissue. Advances in bronchoscopic technologies, particularly endobronchial ultrasound-guided transbronchial needle injection (EBUS-TBNI), robotic bronchoscopy, electromagnetic navigation bronchoscopy, and cone-beam computed tomography guidance, have expanded the feasibility of delivering therapeutic agents to central and peripheral pulmonary lesions. Most of the evidence for ITI comes from case reports, prospective or retrospective studies with small sample sizes, and non-randomized, single-arm clinical trials. While further evidence is needed, especially in the form of randomized controlled trials, the current literature shows promise in the areas of malignant airway obstruction and isolated mediastinal and hilar recurrence. Studies have also assessed the utility of novel formulations, including large surface area microparticle paclitaxel (LSAM-PTX). Potential future applications of ITI include use as neoadjuvant therapy, as part of combination therapy with radiation and immune checkpoint inhibitors, and in cases of oligoprogressive disease and medically inoperable tumors. Novel formulations, including large surface area microparticle paclitaxel (LSAM-PTX), sustained-release drug delivery systems, and the potential use of immunomodulatory agents, have further enhanced the therapeutic potential of local drug administration. Furthermore, advances in radiomics, artificial intelligence, computational drug distribution modeling, and biomarker-driven patient selection have positioned ITI within the broader framework of personalized cancer therapy. This review summarizes the biological rationale, technical approaches, clinical evidence, and future directions of ITI in lung cancer, emphasizing its evolving role as a precision therapeutic platform capable of providing effective cancer treatment alongside established therapeutic paradigms.