The targeted treatment of advanced non-small cell lung cancer (NSCLC) harboring genomic rearrangement of is a paradigm for personalized oncology. More than 15 different ALK fusion partners have been discovered in NSCLC patients. Most of these fusions responded well to the ALK inhibitor crizotinib. Crizotinib is an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced NSCLC harboring ALK rearrangement. An understanding of the mechanisms by which tumors harbor primary drug resistance or acquired resistance to targeted therapies is critical for predicting which patients will respond to a specific therapy and for the identification of additional targetable pathways to maximize clinical benefits. Cap methyltransferase 1() also known as hMTr1, which is translate a human cap1 2'-o-ribose methyltransferase. Here, we report the newly found fusion, , in a patient who has no response to the inhibitor crizotinib. The results remind us that detecting status is important, but that determining the fusion type and function may be more important for patient.
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http://dx.doi.org/10.1080/15384047.2018.1480282 | DOI Listing |
Medicine (Baltimore)
January 2025
Department of Respiratory and Critical Care Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, China.
Rationale: ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported.
View Article and Find Full Text PDFCurr Oncol
December 2024
School of Pharmacy, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
The treatment landscape for patients with advanced ALK-positive NSCLC has rapidly evolved following the approval of several ALK TKIs in Canada. However, public funding of ALK TKIs is mostly limited to the first line treatment setting. Using linked provincial health administrative databases, we examined real-world outcomes of patients with advanced ALK-positive NSCLC receiving ALK TKIs in Ontario between 1 January 2012 and 31 December 2021.
View Article and Find Full Text PDFBlood Adv
January 2025
Stanford University School of Medicine, Stanford, California, United States.
Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL.
View Article and Find Full Text PDFThorac Cancer
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background: The clinical implications of different EML4-ALK fusion variants remain poorly elucidated in the era of second-generation ALK inhibitors.
Methods: This was a retrospective cohort study, wherein patients diagnosed with locally advanced or metastatic non-small cell lung cancer harboring EML4-ALK fusion were stratified into two cohorts based on their first-line treatment: Cohort 1 received alectinib, while Cohort 2 received crizotinib. Statistical analysis was employed to investigate the impact of different EML4-ALK variants and TP53 status on the efficacy of first-line ALK-TKIs.
PLoS One
January 2025
Department of Basic Sciences, Bioethics and Human Life, Faculty of Human Medicine, University of Piura, Miraflores, Lima, Perú.
The anaplastic lymphoma kinase (ALK) oncoprotein plays a crucial role in non-small cell lung cancer (NSCLC) by activating signaling pathways involved in cell proliferation and survival through constitutive phosphorylation. While first-line crizotinib can regulate phosphorylation, mutations in the ALK gene can lead to resistance against ALK inhibitors (ALKi) such as ceritinib and alectinib. On the other hand, overexpression of BCL2, a protein involved in cell death regulation, has been observed in NSCLC and is considered a potential therapeutic target.
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