pf-06463922 has been researched along with Glioma* in 4 studies
4 other study(ies) available for pf-06463922 and Glioma
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Lorlatinib for ALK-fused, infant-type hemispheric glioma with lung metastasis: a case report.
Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis. Topics: Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Child; Glioma; Humans; Infant; Lactams, Macrocyclic; Lung Neoplasms; Protein Kinase Inhibitors | 2023 |
Lorlatinib for the Treatment of ALK Fusion-Positive Infant-Type Hemispheric Glioma: A Case Report.
Topics: Glioma; Humans; Lactams, Macrocyclic; Pyrazoles; Receptor Protein-Tyrosine Kinases | 2022 |
Lorlatinib in a Child with
Topics: Aminopyridines; Anaplastic Lymphoma Kinase; Brain Neoplasms; Child, Preschool; Combined Modality Therapy; Glioma; Humans; Lactams; Lactams, Macrocyclic; Magnetic Resonance Imaging; Neoplasm Recurrence, Local; Pyrazoles; Remission Induction | 2021 |
PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations.
Oncogenic c-ros oncogene1 (ROS1) fusion kinases have been identified in a variety of human cancers and are attractive targets for cancer therapy. The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promising clinical activity in ROS1 fusion-positive non-small cell lung cancer. However, emerging clinical evidence has shown that patients can develop resistance by acquiring secondary point mutations in ROS1 kinase. In this study we characterized the ROS1 activity of PF-06463922, a novel, orally available, CNS-penetrant, ATP-competitive small-molecule inhibitor of ALK/ROS1. In vitro, PF-06463922 exhibited subnanomolar cellular potency against oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1(G2026M) gatekeeper mutation. Compared with crizotinib and the second-generation ALK/ROS1 inhibitors ceritinib and alectinib, PF-06463922 showed significantly improved inhibitory activity against ROS1 kinase. A crystal structure of the PF-06463922-ROS1 kinase complex revealed favorable interactions contributing to the high-affinity binding. In vivo, PF-06463922 showed marked antitumor activity in tumor models expressing FIG-ROS1, CD74-ROS1, and the CD74-ROS1(G2032R) mutation. Furthermore, PF-06463922 demonstrated antitumor activity in a genetically engineered mouse model of FIG-ROS1 glioblastoma. Taken together, our results indicate that PF-06463922 has potential for treating ROS1 fusion-positive cancers, including those requiring agents with CNS-penetrating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation. Topics: Aminopyridines; Animals; Carcinogenesis; Cell Proliferation; Crizotinib; Crystallography, X-Ray; Disease Models, Animal; Drug Resistance, Neoplasm; Glioma; Humans; Lactams; Lactams, Macrocyclic; Mice; Models, Molecular; Mutation; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Pyrazoles; Pyridines; Signal Transduction | 2015 |