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Modulation Of Pi3k-Akt Pathway In Colorectal Cancer, Maliha Nusrat
Modulation Of Pi3k-Akt Pathway In Colorectal Cancer, Maliha Nusrat
Dissertations & Theses (Open Access)
The phosphatidylinositol-3-kinase (PI3K) signaling pathway is activated in 20-40% colorectal cancers (CRC) through PTEN loss (PTENloss) and PIK3CA mutations (PIK3CAmut). Allosteric AKT inhibition with MK2206 monotherapy has been ineffective in CRC patients. We investigated the impact of MK2206 on pharmacodynamic (PD) markers and signaling pathways using reverse phase protein array (RPPA) on (1) paired tumor biopsies from a clinical trial of MK2206 in PI3K-altered metastatic CRC, (2) PTENlossCRC patient derived xenografts (PDX) treated with MK2206 or carrier, and (3) MK2206-treated cell lines. PD inhibition was deep in cell lines, less but significant in …
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti
Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti
Dissertations & Theses (Open Access)
After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …