Publications by authors named "A Vattay"
Uveal melanoma (UM) is the most common primary intraocular malignancy in the adult eye. Despite the aggressive local management of primary UM, the development of metastases is common with no effective treatment options for metastatic disease. Genetic analysis of UM samples reveals the presence of mutually exclusive activating mutations in the Gq alpha subunits GNAQ and GNA11.
View Article and Find Full Text PDFUveal melanoma is a rare and aggressive cancer that originates in the eye. Currently, there are no approved targeted therapies and very few effective treatments for this cancer. Although activating mutations in the G protein alpha subunits, and , are key genetic drivers of the disease, few additional drug targets have been identified.
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- SMARCA2 (BRM) is a key ATPase and member of the SWI/SNF chromatin-remodeling complex, which plays a crucial role in regulating gene expression alongside its relative, BRG1 (SMARCA4).
- Current research highlights the lack of small molecules that can specifically inhibit the ATPase activity of SWI/SNF, despite the relevance in cancer, particularly in BRG1-deficient cases.
- New allosteric dual inhibitors targeting both BRM and BRG1 have been developed, showing potential to reduce BRM-dependent gene expression and demonstrate anti-cancer effects in a BRG1-mutant lung tumor model, providing insights into SWI/SNF functions in various health contexts.
The malignant brain cancer medulloblastoma is characterized by mutations in Hedgehog (Hh) signaling pathway genes, which lead to constitutive activation of the G protein (heterotrimeric guanosine triphosphate-binding protein)-coupled receptor Smoothened (Smo). The Smo antagonist NVP-LDE225 inhibits Hh signaling and induces tumor regression in animal models of medulloblastoma. However, evidence of resistance was observed during the course of treatment.
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