Abstract
BACKGROUND AND OBJECTIVE: Pulmonary sarcomatoid carcinoma (PSC) accounts for approximately 0.5% of non-small cell lung cancer (NSCLC) cases and is thus a rare subtype. Highly aggressive and hard to detect early, PSC responds poorly to surgery, radiotherapy, and chemotherapy. Therefore, this review aims to synthesize current evidence on its pathogenesis and emerging therapeutic strategies, to improve clinical management. METHODS: We searched PubMed for original studies, reviews, clinical trials, and case reports on PSC published until 2025. Moreover, data from ClinicalTrials.gov and major academic conference proceedings were examined for inclusion in this narrative review. KEY CONTENT AND FINDINGS: The core pathophysiology of PSC is epithelial-mesenchymal transition (EMT), a process that drives biphasic differentiation of tumor cells and remodels the tumor microenvironment (TME), thereby promoting high invasiveness and treatment resistance. Therapeutically, although targetable mutations such as MET exon 14 skipping are relatively frequent in PSC, the efficacy of targeted agents is generally inferior to that for other NSCLC subtypes. Notably, the tumor immune microenvironment of PSC features significant immune cell infiltration and high programmed death-ligand 1 (PD-L1) expression, leading to a generally better response to immune checkpoint inhibitors (ICIs). Consequently, immunotherapy combined with chemotherapy or antiangiogenic agents has emerged as a productive therapeutic strategy. CONCLUSIONS: Precision therapy for PSC, particularly immunotherapy-based combination strategies, has demonstrated transformative potential. However, further efforts in this field should involve clarifying the relevant EMT and tumor heterogeneity mechanisms, optimizing existing treatment regimens, and conducting targeted clinical trials, as these measures may advance individualized precision therapy for patients with PSC and improve their outcomes.