Patients with non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping can benefit from crizotinib treatment. Currently, the main resistance mechanisms to crizotinib are MET D1228N and Y1230C mutations. We reported a case of a Chinese NSCLC patient with MET exon 14 skipping detected by targeted next-generation sequencing (NGS) achieved clinical and imaging remission after crizotinib treatment. Then, amplification of multiple genes such as erb-b2 receptor tyrosine kinase 2 (HER2) was detected when disease progressed, indicating novel resistance mechanisms to crizotinib. Ultimately the patient died from cancer-related factors. This was the first NSCLC case with MET exon 14 skipping which reported the HER2 gene amplification at the time of progression during crizotinib treatment, indicating that bypass mechanisms contribute to the development of acquired resistance to MET inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6606013 | PMC |
| http://dx.doi.org/10.1080/15384047.2019.1566049 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
MET Activation in Lung Cancer and Response to Targeted Therapies.
Cancers (Basel)
January 2025
Integrative Oncology, BC Cancer Research Institute, Vancouver, BC V5Z 1L3, Canada.
The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that mediates the activity of a variety of downstream pathways upon its activation. These pathways regulate various physiological processes within the cell, including growth, survival, proliferation, and motility. Under normal physiological conditions, this allows MET to regulate various development and regenerative processes; however, mutations resulting in aberrant MET activity and the consequent dysregulation of downstream signaling can contribute to cellular pathophysiology.
View Article and Find Full Text PDFExploring practical experience with different treatments in NSCLC patients with MET-deregulated: a retrospective analysis from the real world.
BMC Pulm Med
January 2025
Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dong Ming Road, Zhengzhou, 450008, China.
Background: Mesenchymal to epithelial transition factor (MET) dysregulation in non-small-cell-lung-cancer (NSCLC) is understudied, with scant data on treatment outcomes.
Methods: We retrospectively examined 160 NSCLC patients: 125 with primary MET mutations (further classified into MET exon 14 (METex14) skipping mutations and primary MET amplifications) and 35 with secondary MET amplifications. Patients underwent varied treatments: Chemotherapy, Immune monotherapy, Crizotinib, or Savolitinib.
MOMENT registry: Patients with advanced non-small-cell lung cancer harboring exon 14 skipping treated with systemic therapy.
J Comp Eff Res
February 2025
Department of Epidemiology, Merck Healthcare KGaA, Darmstadt, Germany.
exon 14 ex14) skipping occurs in 3-4% of non-small-cell lung cancer (NSCLC) cases. Low frequency of this alteration necessitated open-label, single-arm trials to investigate MET inhibitors. Since broad MET biomarker testing was only recently introduced in many countries, there is a lack of historical real-world data from patients with ex14 skipping NSCLC receiving conventional therapies.
View Article and Find Full Text PDF[A Case Report of EGFR-TKIs Resistant Secondary MET Gene Amplified Lung Squamous Cell Carcinoma and Literature Review].
Zhongguo Fei Ai Za Zhi
November 2024
Department of Oncology, The Central Hospital of Shaoyang, Shaoyang 422000, China.
With the rapid development of epidermal growth factor receptor (EGFR) gene testing of lung adenocarcinoma patients has been routinely carried out, EGFR mutations are also possible for some small samples of non-smoking female lung squamous cell carcinoma patients. This increases the opportunity for targeted therapy for this group of patients. However, drug resistance in patients with lung squamous cell carcinoma during targeted therapy is an important factor affecting subsequent treatment.
View Article and Find Full Text PDF[Savolitinib Induced Pathological Complete Response in Non-small Cell Lung Cancer with MET Amplification: A Case Report].
Zhongguo Fei Ai Za Zhi
November 2024
Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin 300000, China.
Mesenchymal-epithelial transition factor (MET) gene mutation is a large class of mutations commonly seen in non-small cell lung cancer (NSCLC). MET mutation includes subtypes such as MET exon 14 skipping mutation (METex14m) and MET amplification (METamp). For advanced NSCLC with METex14m, Savolitinib has a high sensitivity as a member of tyrosine kinase inhibitors (TKIs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!