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Full-Text Articles in Medicine and Health Sciences
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady
Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady
Dissertations & Theses (Open Access)
Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α …
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 …
Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin
Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin
Theses and Dissertations--Pharmacy
Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …