Publications by authors named "P Coffino"
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis.
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- * This study introduces a novel PROTAC called StIP-TAC, which recruits E3 ligase to Protein Kinase A (PKA) using a hydrocarbon-stapled peptide, effectively promoting the degradation of PKA.
- * Treatment with StIP-TAC not only induced the degradation of PKA but also significantly reduced its activity by lowering phosphorylation of its substrates, suggesting that this approach can potentially target a wider range of proteins lacking suitable small molecule binding sites.
Article Synopsis
- Fibrolamellar hepatocellular carcinoma (FLC) is a rare type of liver cancer caused by a fusion of specific genes.
- Researchers found that in FLC, there is a higher ratio of active protein to regulatory proteins, which can cause the cancer to grow and spread.
- Changes in how a protein called PKA works and where it is located in the cell are more important for this cancer than the specific gene fusion itself.
Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis.
View Article and Find Full Text PDFFibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia.
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