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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Friday, October 24, 2025
Sara Pilotto, MD, PhD, of the University of Verona, Italy, and colleagues conducted a study to investigate the impact of tumor suppressor gene alterations on the outcomes of patients with advanced non–small cell lung cancer (NSCLC) in a real-world setting. Their findings were published in the journal Scientific Reports.
“Extended comprehensive genomic profiling, encompassing tumor suppressor gene alterations, provides valuable prognostic and predictive insights for advanced NSCLC, thereby adding to the mere identification of potential targets for targeted therapy,” the investigators commented. “Our findings also underline the complexity of the lung cancer molecular landscape and suggest the need for studying a personalized therapeutic approach in patients with tumor suppressor gene alterations.”
A total of 201 patients were included in the analysis. The investigators interrogated the IMMINENT clinical-genomic database—which includes anonymized patient-level data from individuals with advanced NSCLC who underwent comprehensive genomic profiling by tissue- or blood-based next-generation sequencing between May 2019 and November 2022—to assess overall and progression-free survival. Using the Cox proportional hazard model, they assessed the prognostic and predictive role of genomic features.
The investigators reported that alterations in STK11, KEAP1, and MYC were linked to poorer overall survival, whereas ALK alterations were found to be associated with more favorable outcomes. After adjustment, STK11 and KEAP1 alterations seemed to retain their independent negative prognostic impact. Furthermore, co-mutations of KRAS:STK11 and KRAS:KEAP1 cooperated to negatively influence overall survival. Regarding predictive performance, CDKN2A/B and TP53 alterations were found to predict worse progression-free survival on chemotherapy and targeted therapy, respectively. In contrast, these alterations, as well as those in KRAS, seemed to be associated with improved progression-free survival on immunotherapy.
Disclosure: The study's authors reported no conflicts of interest.
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