H3 Biomedicine

Intron Retention Is a Hallmark and Spliceosome Represents a Therapeutic Vulnerability in Aggressive Prostate Cancer

The role of dysregulation of mRNA alternative splicing (AS) in the development and progression of solid tumors remains to be… Read More

Metabolic Disposition of H3B-8800, an Orally Available Small-Molecule Splicing Modulator, in Rats, Monkeys, and Humans

H3B-8800, a novel orally available modulator of the SF3b complex, which potently and preferentially kills spliceosome-mutant tumor cells, is in… Read More

Sensitivity to Splicing Modulation of BCL2 Family Genes Defines Cancer Therapeutic Strategies for Splicing Modulators

Dysregulation of RNA splicing by spliceosome mutations or in cancer genes is increasingly recognized as a hallmark of cancer. Small… Read More

Splicing Modulation as Novel Therapeutic Strategy Against Diffuse Malignant Peritoneal Mesothelioma

Introduction: Therapeutic options for diffuse malignant peritoneal mesothelioma (DMPM) are limited to surgery and locoregional chemotherapy. Despite improvements in survival… Read More

Splicing Modulation Sensitizes Chronic Lymphocytic Leukemia Cells to Venetoclax by Remodeling Mitochondrial Apoptotic Dependencies

The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected… Read More

Synthetic Lethal and Convergent Biological Effects of Cancer-Associated Spliceosomal Gene Mutations

Mutations affecting RNA splicing factors are the most common genetic alterations in myelodysplastic syndrome (MDS) patients and occur in a… Read More

Structural Basis of Splicing Modulation by Antitumor Macrolide Compounds

SF3B is a multi-protein complex essential for branch site (BS) recognition and selection during pre-mRNA splicing. Several splicing modulators with… Read More

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences Across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of… Read More

The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action

Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic… Read More

H3B-8800, an orally available small-molecule splicing modulator, induces lethality in spliceosome-mutant cancers

Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor–encoding genes SF3B1, U2AF1, and SRSF2 that… Read More