The steady increase in global cancer burden has fuelled the development of several modes of treatment for the disease. In the presence of an actionable mutation, targeted therapies offer a method to selectively attack cancer cells, increasing overall efficacy and reducing harmful side effects. However, different drug molecules are in different stages of development, with new molecules obtaining approvals from regulatory agencies each year. To augment clinical impact, it is important that this information reaches clinicians, patients and researchers swiftly and in a structured, well-annotated manner. To this end, we have developed Mutation-Specific Therapies Resource and Database in Cancer (MUSTARD), a database that is designed to be a centralized resource with diverse information such as cancer subtype, associated mutations, therapy offered and its effect observed, along with links to external resources for a more comprehensive annotation. In its current version, MUSTARD comprises over 2105 unique entries, including associations between 418 unique drug therapies, 189 cancer subtypes and 167 genes curated and annotated from over 862 different publications. To the best of our knowledge, it is the only resource that offers comprehensive information on mutation-specific, gene fusions and overexpressed gene-targeted therapies for cancer. Database URL: http://clingen.igib.res.in/mustard/.
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http://dx.doi.org/10.1093/database/baab042 | DOI Listing |
Hemasphere
December 2024
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty RWTH Aachen University Aachen Germany.
Myelofibrosis (MF) is a clonal myeloid neoplasm characterized by bone marrow fibrosis, splenomegaly, and disease-associated symptoms, as well as increased mortality, due to thrombosis, severe bleeding, infections, or progression to acute leukemia. Currently, the management of MF patients is tailored according to risk scores, with higher-risk (intermediate-2 and high-risk) patients being assessed for allogeneic stem cell transplantation, which remains the only potentially curative treatment option. On the other hand, lower risk (low- and intermediate-1 risk) patients who are symptomatic may be treated with JAK inhibitors or other drugs.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2024
Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada; Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada. Electronic address:
Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome associated with a highly penetrant cancer spectrum characterized by germline TP53 mutations. We characterized the first LFS zebrafish hotspot mutants, tp53 R217H and R242H (human R248H and R273H), and found these mutants exhibit partial-to-no activation of p53 target genes, have defective cell-cycle checkpoints, and display partial-to-full resistance to apoptosis, although the R217H mutation has hypomorphic characteristics. Spontaneous tumor development histologically resembling human sarcomas was observed as early as 6 months.
View Article and Find Full Text PDFbioRxiv
November 2024
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Expert Opin Investig Drugs
December 2024
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Genes (Basel)
November 2024
Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Background/objectives: Antisense oligonucleotide (ASO)-mediated exon-skipping is an effective approach to restore the disrupted reading frame of the dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Currently, four FDA-approved ASOs can target three different exons, but these therapies are mutation-specific and only benefit a subset of patients. Understanding the broad applicability of exon-skipping approaches is essential for prioritizing the development of additional therapies with the greatest potential impact on the DMD population.
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