Oncogenic Addictions in Advanced NSCLC: Clinical Insights from Routine Molecular Profiling
DOI:
https://doi.org/10.61424/ijmhr.v4i3.1006Keywords:
NSCLC, Oncogenic drivers, Precision medicine, Targeted therapyAbstract
Non-small cell lung cancer (NSCLC) exhibits significant molecular heterogeneity. Identifying oncogenic alterations is now a cornerstone of advanced disease management, facilitating access to targeted therapies. This study aimed to delineate the molecular landscape of NSCLC and evaluate the prevalence of major oncogenic drivers in our routine clinical practice. We conducted a retrospective analysis of 127 patients diagnosed with stage III or IV NSCLC between June 2023 and June 2025. Demographic, histological, and smoking history data were extracted. Molecular profiling focused primarily on EGFR mutations, alongside ALK and ROS1 rearrangements. The cohort had a mean age of 65.6 years (range: 30–88), with a strong male predominance (89.8%). Most patients (69.3%) reported a smoking history. Adenocarcinoma was the leading histology (70.1%), followed by squamous cell carcinoma (22.0%). Among the 59 patients tested for EGFR, mutations were detected in 16.9% (n=10). ALK and ROS1 rearrangements were identified in 7 and 6 patients, respectively, including 2 cases of ALK/ROS1 co-alteration. These results underscore the actionable mutational burden within this specific population. Systematic molecular profiling is imperative in advanced NSCLC. The detection of specific oncogenic drivers allows for the concrete integration of precision medicine and optimizes the selection of candidates for targeted therapies. Broadening the scope of routine molecular testing remains a critical priority to improve therapeutic outcomes.
References
Barlesi F, Mazieres J, Merlio JP, Debieuvre D, Mosser J, Lena H (2016). Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet. 387(10026):1415-26.
Cai W, Lin P, Zhu L, Zhang X, Guo L, Li J (2019). ALK rearrangements co-existing with EGFR mutations in non-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer. 130:14-21.
de Groot PM, Wu CC, Sluiter WJ, Groen HJ (2019). Incidence and prediction of interval lung cancer in a screened population: The NELSON study. J Thorac Oncol. 14(9):1546-53.
Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman JR, Bharat A, (2022). Non-Small Cell Lung Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 20(5):497-530.
Lepage C, Bouchard G, Lacombe J, Barfett J, Brouard S, Didier R, (2022). Real-world testing for actionable mutations in non-small-cell lung cancer: A systematic review. Lung Cancer. 172:1-8.
Lindeman NI, Cagle PT, Aisner DL, Arcila ME, Beasley MB, Bernicker EH, (2018). Molecular testing guideline for selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors: American Society of Clinical Oncology/COLLEGE OF AMERICAN PATHOLOGISTS clinical practice guideline update. J Clin Oncol. 36(9):911-29.
Lortet-Tieulent J, Soerjomataram I, Ferlay J, Rutherford M, Bray F (2014). International trends in lung cancer incidence by histological subtype: adenocarcinoma stabilizing in men but still increasing in women. Lung Cancer. 84(1):13-8.
Midha A, Dearden S, McCormack R. (2015). EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 5(9):2892-911.
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361(10):947-57.
Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C (2018). Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 29(Suppl 4):iv192-237.
Sharma SV, Bell DW, Settleman J, Haber DA (2007). Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007;7(3):169-81.
Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T (2014). First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 371(23):2167-77.
Soria JC, Tan DSW, Chiari R, Wu YL, Paz-Ares L, Wolf J (2023). First-line osimertinib uncompromised by concurrent TP53 mutations in EGFR-mutant NSCLC. J Thorac Oncol. 2023;18(5):609-18.
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71(3):209-49.
Wood DE, Kazerooni EA, Baum SL, Dransfield MT, Eapen GA, Ettinger DS (2018). Lung cancer screening, version 3.2018: NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2018;16(4):412-41.
Zhang Y, Zhang J, Gao J, Liu B, Wang Y, Li Y (2019). Co-occurrence of ALK and ROS1 rearrangements in lung adenocarcinoma: a case report and literature review. Oncol Lett. 17(5):4733-8.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Assia BENSALEM, Abdelaziz AMMARI, Rahma DJOUABI
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
