Publications by authors named "Monica Vishnu Valecha"

Sleeping Beauty (SB) insertional mutagenesis has been widely used for genome-wide functional screening in mouse models of human cancers, however, intertumor heterogeneity can be a major obstacle in identifying common insertion sites (CISs). Although previous algorithms have been successful in defining some CISs, they also miss CISs in certaations. A major common characteristic of these previous methods is that they do not take tumor heterogeneity into account.

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Article Synopsis
  • - Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia with varying subtypes that show different molecular characteristics, drug responses, and sensitivity to radiation treatment.
  • - The epithelial carcinoma (EC) subtype is linked to issues with cell division and microtubule function, while sarcomatoid (SC) and mixed subtypes (MSEC) have genes associated with cell movement and invasion.
  • - By using patient-derived organoids, the study identifies subtype-specific treatments: SC and MSEC respond well to microtubule inhibitors, and EC responds better to EGFR inhibitors, especially when combined with radiotherapy.
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BRCA1 mutation carriers have a higher risk of developing triple-negative breast cancer (TNBC), which is a refractory disease due to its non-responsiveness to current clinical targeted therapies. Using the Sleeping Beauty transposon system in Brca1-deficient mice, we identified 169 putative cancer drivers, among which Notch1 is a top candidate for accelerating TNBC by promoting the epithelial-mesenchymal transition (EMT) and regulating the cell cycle. Activation of NOTCH1 suppresses mitotic catastrophe caused by BRCA1 deficiency by restoring S/G2 and G2/M cell cycle checkpoints, which may through activation of ATR-CHK1 signalling pathway.

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