Publications by authors named "Mythili Merchant"
Article Synopsis
- - The study identifies zotiraciclib (ZTR) as a potent treatment for IDH-mutant gliomas, showing it selectively inhibits their growth through a targeted approach.
- - ZTR works by suppressing key proteins involved in cell function, leading to mitochondrial dysfunction, reduced NAD+ production, and increased oxidative stress.
- - These findings have prompted a clinical trial (NCT05588141) to explore the effectiveness of ZTR in treating patients with IDH-mutant gliomas, reflecting a move toward precision medicine.
Article Synopsis
- Deletions or mutations in the PTEN gene are common in glioblastoma (GBM) and lead to issues with DNA damage repair; this study investigates whether PTEN deficiency creates a weakness against combined DNA damage and repair suppression using specific inhibitors.
- Researchers treated different GBM cell lines with the drug LMP400 (a TOP1 inhibitor) alone and with either PARP inhibitors (Olaparib or Niraparib) and found that PTEN-null cells are significantly more sensitive to this treatment.
- The combination of LMP400 and Niraparib not only increases cell death in PTEN-deficient glioma cells but also shows promise in animal models for penetrating the blood-brain barrier and improving survival, supporting the
Most tumors, including brain tumors, are sporadic. However, a small subset of CNS tumors are associated with hereditary cancer conditions like Lynch Syndrome (LS). Here, we present a case of an oligodendroglioma, IDH-mutant and 1p/19q-codeleted, and LS with a germline pathogenic mutation.
View Article and Find Full Text PDFBackground: A consistent correlation between tumor mutation burden (TMB) and tumor immune microenvironment has not been observed in gliomas as in other cancers.
Methods: Driver germline and somatic mutations, TMB, neoantigen, and immune cell signatures were analyzed using whole exome sequencing (WES) and transcriptome sequencing of tumor and WES of matched germline DNA in a cohort of 66 glioma samples (44 IDH-mutant and 22 IDH-wildtype).
Results: Fourteen samples revealed a hypermutator phenotype (HMP).
Tumor mutational burden (TMB) is an emerging biomarker for the prediction of immunotherapy success in solid tumors. Gliomas, however, do not demonstrate a correlation between TMB and immunotherapy efficacy. Here, we discuss the potential factors influencing this discordance, focusing on the impact of neoantigen immunogenicity, clonality, expression, and presentation.
View Article and Find Full Text PDFGlioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients.
View Article and Find Full Text PDF