Publications by authors named "Laura Baldino"
Unlabelled: The phosphoinositide 3-kinase (PI3K) pathway regulates proliferation, survival, and metabolism and is frequently activated across human cancers. A comprehensive elucidation of how this signaling pathway controls transcriptional and cotranscriptional processes could provide new insights into the key functions of PI3K signaling in cancer. Here, we undertook a transcriptomic approach to investigate genome-wide gene expression and transcription factor activity changes, as well as splicing and isoform usage dynamics, downstream of PI3K.
View Article and Find Full Text PDFOn-target resistance to next-generation TRK inhibitors in TRK fusion-positive cancers is largely uncharacterized. In patients with these tumors, we found that TRK xDFG mutations confer resistance to type I next-generation TRK inhibitors designed to maintain potency against several kinase domain mutations. Computational modeling and biochemical assays showed that TRKA and TRKC xDFG substitutions reduce drug binding by generating steric hindrance.
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- The HER2 gene mutations and amplifications lead to increased tumor growth by hyperactivating the HER2 receptor tyrosine kinase, but its internalization and ubiquitination are crucial for the effectiveness of certain anti-HER2 therapies, particularly in lung cancer.
- A clinical trial showed a 51% response rate for the drug ado-trastuzumab emtansine (T-DM1) in non-small cell lung cancer patients with HER2 alterations, and using irreversible pan-HER inhibitors can further improve treatment outcomes.
- Switching from T-DM1 to trastuzumab deruxtecan (T-DXd) offers durable responses in cases where resistance develops, indicating potential advancements in the