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Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile.

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Molecular Pharmacology of Dasatinib Provides Unique Insights into the Mechanistic Basis of Success and Failure of Targeted Cancer Therapy.

ACS Pharmacol Transl Sci

January 2025

Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Rd, Kingston, Rhode Island 02881, United States.

Despite the enthusiasm for targeted cancer therapies in preclinical studies and the success of a select few drugs, many promising drug candidates fail in clinical trials. The gap between preclinical promise and clinical outcomes underscores the need to investigate factors influencing the success or failure of targeted therapies. Dasatinib, an inhibitor of Abl and Src protein tyrosine kinases, is highly effective toward chronic myeloid leukemia (CML) by targeting BCR-Abl, but it is ineffective against solid tumors when targeting Src kinases.

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Dual sgRNA-directed knockout gene expression using CRISPR/Cas9 technology for editing gene in triple-negative breast cancer.

Narra J

December 2024

Animal Research Facilities, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) offers a robust approach for genome manipulation, particularly in cancer therapy. Given its high expression in triple-negative breast cancer (TNBC), targeting with CRISPR/Cas9 holds promise as a therapeutic strategy. The aim of this study was to design specific single guide ribonucleic acid (sgRNA) for CRISPR/Cas9 to permanently knock out the gene, exploring its potential as a therapeutic approach in breast cancer while addressing potential off-target effects.

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Background: Hepatocellular carcinoma (HCC) constitutes approximately 75-85% of primary liver cancers and is a heavy burden on public health. Many innovative prediction systems have integrated radiomics, artificial intelligence, pathological information, or even genetic information for the stratification and prognosis prediction of patients with HCC. However, these systems still lack practical and clinical applications.

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Background: At present, there is a dearth of objective methodologies for assessing the effectiveness of treatments for Lateral Epicondylitis (LE). This study examined 73 patients suffering from tennis elbow using a multimodal ultrasound approach and investigated the correlation between pertinent indicators and clinical scores.

Methods: 73 patients diagnosed with unilateral tennis elbow by interventional ultrasound at Zhejiang Rongjun Hospital were included in the study.

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