Publications by authors named "Benjamin T Whitfield"
Article Synopsis
- Inactivation of the ATRX gene is a key feature of malignant gliomas, leading to G-quadruplex (G4) DNA structures that cause replication stress and genomic instability.
- The study tested a drug, CX-5461, on glioma stem cells and mouse models, both alone and with radiation, showing it was particularly effective against ATRX-deficient tumors.
- The results revealed that CX-5461 increased DNA damage and cell death specifically in ATRX-deficient models, reduced tumor growth, and improved survival in mice, highlighting its potential as a new treatment approach for this type of cancer.
Unlabelled: Lack of robust activation of Stimulator of Interferon Genes (STING) pathway and subsequent induction of type I IFN responses is considered a barrier to antitumor immunity in acute myeloid leukemia (AML). Using common human AML cell lines as in vitro tools to evaluate the efficacy of novel STING agonists, we found most AML lines to be poor producers of IFNs upon exposure to extremely potent agonists, suggesting cell-intrinsic suppression of STING signaling may occur. We observed unexpected patterns of response that did not correlate with levels of STING pathway components or of known enzymes associated with resistance.
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- Researchers are investigating how stimulating the innate immune system could help treat gliomas, especially focusing on the interaction between ATRX mutations and IDH mutations.
- ATRX-deficient glioma models show increased sensitivity to dsRNA treatments, leading to reduced tumor lethality and higher T-cell infiltration, but IDH1 mutations negatively affect immune gene expression.
- IDH1 doesn't prevent the sensitivity to dsRNA, but it does diminish the immune response, suggesting that targeting innate immunity could be a promising therapeutic strategy for astrocytomas.
Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in , defining molecular alterations in -mutant astrocytomas, have been implicated in dysfunctional immune signaling. However, little is known about the interplay between ATRX loss and mutation on innate immunity.
View Article and Find Full Text PDFOver the last decade, developments in molecular profiling have radically altered the diagnosis, classification, and management of numerous cancer types, with primary brain tumors being no exception. Although historically brain tumors have been classified based on their morphological characteristics, recent advances have allowed refinement of tumor classification based on molecular alterations. This shift toward molecular classification of primary brain tumors is reflected in the 2021 5 edition of the WHO classification of central nervous system tumors (WHO 2021).
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