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The Revolution in Pharmacotherapy: From Herbs to Pills, Molds, Antibodies to Genetic Tools.
Eur Heart J Cardiovasc Pharmacother
January 2025
Director of Research, Education & Development, Heart Division, Royal Brompton and Harefield Hospitals GSTT, Sydney Street. London SW 3 6NP, UK.
First-in-human phase I trial of the bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, SL-172154 in patients with platinum-resistant ovarian cancer.
J Immunother Cancer
January 2025
Medical Oncology, Sarah Cannon Research Institute, Nashville, Tennessee, USA.
Background: SL-172154 is a hexameric fusion protein adjoining the extracellular domain of SIRPα to the extracellular domain of CD40L via an inert IgG-derived Fc domain. In preclinical studies, a murine equivalent SIRPα-Fc-CD40L fusion protein provided superior antitumor immunity in comparison to CD47- and CD40-targeted antibodies. A first-in-human phase I trial of SL-172154 was conducted in patients with platinum-resistant ovarian cancer.
View Article and Find Full Text PDFLow Bacterial Biomass in Human Pancreatic Cancer and Adjacent Normal Tissue.
Int J Mol Sci
December 2024
Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
The gut microbiome plays an important role in the carcinogenesis of luminal gastrointestinal malignancies and response to antineoplastic therapy. Preclinical studies have suggested a role of intratumoral gammaproteobacteria in mediating response to gemcitabine-based chemotherapy in pancreatic ductal adenocarcinoma (PDAC). To our knowledge, this is the first study to evaluate the impact of the PDAC microbiome on chemotherapy response using samples from human pancreatic tumor resections.
View Article and Find Full Text PDFHydroxychloroquine prevents resistance and potentiates the antitumor effect of SHP2 inhibition in NF1-associated malignant peripheral nerve sheath tumors.
Proc Natl Acad Sci U S A
January 2025
Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas and the primary cause of mortality in patients with neurofibromatosis type 1 (NF1). These malignancies develop within preexisting benign lesions called plexiform neurofibromas (PNs). PNs are solely driven by biallelic loss eliciting RAS pathway activation, and they respond favorably to MEK inhibitor therapy.
View Article and Find Full Text PDFKRAS Mutation Status and Treatment Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma.
JAMA Netw Open
January 2025
Huntsman Cancer Institute, University of Utah Health Care, Salt Lake City.
Importance: Despite the high prevalence of KRAS alterations in pancreatic ductal adenocarcinoma (PDAC), the clinical impact of common KRAS mutations with different cytotoxic regimens is unknown. This evidence is important to inform current treatment and provide a benchmark for emergent targeted KRAS therapies in metastatic PDAC.
Objective: To assess the clinical implications of common KRAS G12 mutations in PDAC and to compare outcomes of standard-of-care multiagent therapies across these common mutations.
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