Background: The emergence of secondary drug resistance when treating epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) using EGFR-tyrosine kinase inhibitors (EGFR-TKIs), seriously affects the therapeutic efficacy and survival of patients. Here, we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.
Case Summary: A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma, and exhibited the development of a T790M mutation during initial TKI treatment. Following 3 mo of Osimertinib treatment, a mixed response was observed. Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer (SCLC) harboring RB1 and TP53 mutations, with loss of the original T790M mutation. A standard chemotherapy regimen with Anlotinib for SCLC was administered. Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression. The patient's overall survival was 24 mo.
Conclusion: Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making. Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.
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http://dx.doi.org/10.12998/wjcc.v10.i9.2836 | DOI Listing |
Explor Target Antitumor Ther
November 2024
Department of Medicine, Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Lung cancer is the leading cause of cancer mortality globally, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, creating a significant unmet need for effective second-line therapies. This review evaluates current and emerging second-line therapeutic options for advanced or metastatic NSCLC, focusing on their efficacy and potential to improve patient outcomes.
View Article and Find Full Text PDFJ Drug Target
January 2025
Department of Pharmacology, Orotta College of Medicine and Health Sciences, Asmara University, Asmara, P.O. Box: 10549, Eritrea; (I.P).
Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates "RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK" pathways, which enhance cell division, survival, angiogenesis, and tumor growth while inhibiting apoptosis and metastasis. Secondary mutations (e.
View Article and Find Full Text PDFJ Natl Compr Canc Netw
December 2024
1Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
EGFR tyrosine kinase inhibitors (TKIs) have significantly improved clinical outcomes for patients with non-small cell lung cancer (NSCLC) harboring EGFR-activating mutations. However, resistance to TKI therapy often develops due to secondary EGFR mutations or the activation of bypass signalling pathways. Next-generation sequencing (NGS) can efficiently identify actionable genetic alterations throughout treatment.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Pharmaceutical Chemistry, Division of Computer-Aided Drug Design, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India.
A series of 2,4-disubstituted pyrimidine derivatives bearing 5-substituted-1,3,4 thidiazole were devised and synthesized based on the binding mode of the approved drug Osimertinib with the ATP competitive site of EGFR-L858R/T790M in order to increase selectivity towards double mutant EGFR and potent antitumor activity. Their cellular bioactivity and corresponding enzyme inhibition were studied, and it was revealed that several compounds had significant biological activity and selectivity when compared to the control compounds. One of the most promising compound 8, substantially suppressed the proliferation of H1975 cells and showed significant inhibition of double mutant EGFR-L858R/T790M TK with IC values of 0.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Background: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those lacking the EGFR. IMpower 150 study demonstrated promising efficacy for a combination of immune-chemotherapy and bevacizumab in patients with EGFR-mutated NSCLC.
Methods: This open-label, single-arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.
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