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While significant advancements have been made in the available therapies for metastatic non-small cell lung cancer (NSCLC), acquired resistance remains a major barrier to treatment. We have not yet achieved the ability to cure advanced NSCLC with systemic therapy, despite our growing understanding of many of the oncogenic drivers of this disease. Rather, the emergence of drug-tolerant and drug-resistant cells remains the rule, even in the face of increasingly potent targeted therapies. In this review, we provide a broad overview of the mechanisms of resistance to targeted therapy that have been demonstrated across molecular subtypes of NSCLC, highlighting the dynamic interplay between driver oncogene, bypass signaling pathways, shifting cellular phenotypes, and surrounding tumor microenvironment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675642 | PMC |
http://dx.doi.org/10.1016/j.pharmthera.2020.107522 | DOI Listing |
Zhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of nursing, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510000, China.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) are important treatments for EGFR mutant non-small cell lung cancer (NSCLC). However, the first and second generation EGFR-TKI face clinical limitations due to acquired resistance, such as the T790M mutation. Irreversible EGFR-TKI can significantly prolong the survival of patients by enhancing the inhibition of drug-resistant mutations through the covalent binding mechanism.
View Article and Find Full Text PDFZhonghua Jie He He Hu Xi Za Zhi
September 2025
Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210009, China.
Severe pneumonia, as a critical and prevalent condition of the respiratory system, poses a significant threat to patient survival and health outcomes. This article focuses on the similarities and differences between community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP). There is significant divergence in the predominant pathogens between severe community-acquired pneumonia (SCAP) and HAP/VAP.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Shanghai, 200080, PR China; Shanghai Eye Diseases Prevention &Treatment Center/Shanghai Eye Hospital, School of Medicine, Tongji University, PR China. Electronic address
While vault RNA1-1 (vtRNA1-1) has been implicated in tumor biology, its specific role in cancer stemness and regorafenib resistance remains unexplored. In this study, we identify vtRNA1-1 as a critical regulator of cancer stemness and chemoresistance in Hepatocellular carcinoma (HCC). vtRNA1-1 enhances stemness properties by modulating the nuclear accumulation of Nanog, a core transcription factor.
View Article and Find Full Text PDFBiochem Soc Trans
September 2025
Department of Biochemistry, McGill University, Montréal, QC, Canada.
The MET receptor tyrosine kinase is a pivotal regulator of cellular survival, motility, and proliferation. Mutations leading to skipping of exon 14 (METΔex14) within the juxtamembrane domain of MET impair receptor degradation and prolong oncogenic signaling, contributing significantly to tumor progression across multiple cancer types. METΔex14 mutations are associated with aggressive clinical behavior, therapeutic resistance, and poor outcomes.
View Article and Find Full Text PDFAntimicrob Agents Chemother
September 2025
GSK, London, United Kingdom.
Two recent Phase 3 trials demonstrated the efficacy of gepotidacin compared with nitrofurantoin to treat uncomplicated urinary tract infections (uUTIs) in females. Pretreatment urine specimens were obtained from all participants. Based on pooled trial data (treatment groups combined), central laboratory culture results identified 1,421 (45%) participants with ≥1 baseline qualifying (≥10 CFU/mL) uropathogen (i.
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