P1.03-012 Using Computational Modeling to Simulate Clinical Response of ALK Inhibitors to G1202R ALK and Possible Mechanisms of Resistance
نویسندگان
چکیده
منابع مشابه
Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer
The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant pat...
متن کاملALK mutations conferring differential resistance to structurally diverse ALK inhibitors.
PURPOSE EML4-ALK fusions define a subset of lung cancers that can be effectively treated with anaplastic lymphoma kinase (ALK) inhibitors. Unfortunately, the duration of response is heterogeneous and acquired resistance limits their ultimate efficacy. Thus, a better understanding of resistance mechanisms will help to enhance tumor control in EML4-ALK-positive tumors. EXPERIMENTAL DESIGN By ap...
متن کاملUpdated Evidence on the Mechanisms of Resistance to ALK Inhibitors and Strategies to Overcome Such Resistance: Clinical and Preclinical Data.
Anaplastic lymphoma kinase(ALK) rearrangement is one of the oncogenes in non-small cell lung cancer (NSCLC) identified in 2007. The PROFILE trials demonstrated that patients with ALK-rearranged NSCLC can be successfully treated with crizotinib, and that crizotinib is superior to chemotherapy in both first- and second-line settings. Furthermore, next-generation ALK inhibitors, such as alectinib ...
متن کاملA novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors.
Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers. However, their efficacy will ultimately be limited by the development of acquired drug resistance. Here we report two mechanisms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung...
متن کاملPulmonary Sarcomatoid Carcinoma with ALK Rearrangement: Frequency, Clinical-Pathologic Characteristics, and Response to ALK Inhibitor1
PURPOSE The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this ...
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ژورنال
عنوان ژورنال: Journal of Thoracic Oncology
سال: 2017
ISSN: 1556-0864
DOI: 10.1016/j.jtho.2017.09.816