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Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.
J Immunother Cancer
January 2025
Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.
Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.
Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer.
J Med Chem
January 2025
Scorpion Therapeutics, 1 Winthrop Square, Boston, Massachusetts 02110, United States.
After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge.
View Article and Find Full Text PDFDual VEGFR-2 and EGFR inhibitors of phenyldiazenes: anticancer evaluations, ADMET, docking, design and synthesis.
Future Med Chem
January 2025
Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.
Aim: New phenyldiazene scaffold-linked heterocyclic pyrazole, pyrimidinone, pyrimidinthione, and/or triazine rings have been developed and synthesized.
Methods & Results: Cytotoxicity of our derivatives was estimated on four cancer and VERO normal cell lines targeting EGFR (epidermal growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) enzymes. Our new derivatives selectively inhibited both VEGFR-2 and EGFR as they have the essential structural requirements for inhibitors of both receptors.
Oral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series.
Curr Ther Res Clin Exp
December 2024
Department of Critical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Background: Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.
Objective: This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).
Methods: We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution.
Neratinib and the Role of Anti-HER2 Therapy in Salivary Duct Carcinoma.
Cancer Rep (Hoboken)
January 2025
Department of Oncology and Hematology, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.
Backgroud: Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with a generally dismal prognosis and no standard of care established, despite a known association with epidermal growth factor receptor 2 (HER2) and androgen receptor (AR) over-expression.
Case: We report the case of a 64-year-old female with extra- and intracranial metastases of SDC with evidence of AR and HER2 overexpression. After progression on first line chemotherapy, was administered neratinib, a pan-Erb2 receptor tyrosine kinase inhibitor.
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