Molecular Mechanisms and Potential Predictive Biomarkers in Advanced Non-small Cell Lung Cancer: A Summary of Current and Future Trends
Published on: 27th June, 2024
Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.
Pulmonary Pleomorphic Carcinoma: A Rare Entity Revisited!
Published on: 4th June, 2025
Introduction: Pleomorphic Carcinoma (PC) is a subset of poorly differentiated non–small cell lung cancer that is diagnostically challenging because it is a rare malignancy of the lung. It shows varying dual-cell components; spindle or giant cells and epithelial cells.Method: We report a case of 68-year-old non-smoking female who presented with cough, fever, pain in the left side of chest & weight loss of recent onset and an abnormal shadow on her chest X-ray. Computed tomography of chest revealed a well defined heterogeneously enhancing cavitatory soft tissue lesion in the posterior basal segment of the left lower lobe with mediastinal lymphadenopathy.Results: Fine needle aspiration cytology& percutaneous lung biopsy confirmed poorly differentiated malignant tumor. Patient underwent a left lower lobectomy. A diagnosis of PC was confirmed after Immunohistochemistry (IHC). Mutation analysis revealed an EGFR exon 21 mutation within the tumor cells. The patient is on Gefitinib based chemotherapy and has remained disease-free for three years post-surgery.Conclusion: PC of the lung is a rare pathological entity. Definite diagnosis may only be made on a resected tumor along with the use of IHC. Surgical resection is the main modality of the treatment. Such rare cases should be documented to establish an optimal management plan and to provide a further insight to targeted therapy.
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