To examine the combinatorial therapeutic effects of EGFR inhibitor and mTORC2 inhibitor for treatment of pancreatic cancer

dc.contributorGao, Xiaolian
dc.contributor.authorModi, Paulomi
dc.contributor.authorVo, Henry
dc.contributor.authorRobertson, Celise
dc.description.abstractThe role of protein expression and signaling pathways in cancer cells going under drug treatment has become apparent. It could yield significant insight into developing therapeutic response/ treatment of the diseases. A contributor of pancreatic cancer cell advancement and growth is the inflection of the protein expression and cell signaling pathway. This is a result of the mis-synchronization of protein kinase activity. Transformation of oncogenes can be caused due to mutations in kinase encoded genes. These genes are frequently found in cancer. Kinase inactivation occurs by the actions of these molecules as they are competing with ATP binding to the enzyme allosteric sites. Hence, they disturb cellular signaling pathways resulting in cancer cell growth and survival to deter. As a result, for this experiment, the is target mTORC2 pathway with inhibitors along with various EGFR inhibitors. MTT cell proliferation data represented with the Q curve shows a significant decrease in cell viability when treated with the combination of EGFR and mTORC1/mTORC2 inhibitors. The EGFR inhibitors cause a reduced downstream regulation of PI3K/Akt/mTOR signaling by inhibiting the EGFR phosphorylation. Afatinib is shows inhibitions of EGFR and HER2. Erlotinib and AZD9291 only inhibit EGFR.AZD8055 (mTORC1/mTORC2 inhibitor) that prevents the growth pancreatic cancer cells in combination with EGFR inhibitors (Erlotinib, Afatinib, AZD9291).Combinatorial treatment with EGFRi (Erlotinib, Afatinib, or AZD9291) and mTORi (AZD8055) improved anti-proliferative effects on BxPC-3 cell as compared to EGFRi treatment alone. This combination is shown to be synergetic by Chou and Talalay method, showing high synergetic drug combination at and above IC50. Furthermore, the relative importance of this study, it is important to look at the proteomic complexity and the respective modulating signaling networks. They are derived from alterations in the oncogenes. The therapeutic treatments and resistant mechanisms needed for these alterations have not been fully understood. This presents us with the critical requirement- to minimize the adverse effects of the therapeutic responses and increase drug resistance towards the cancer cells. Thus, the ultimate goal is to enhance treatment efficacy.
dc.description.departmentBiology and Biochemistry, Department of
dc.description.departmentHonors College
dc.relation.ispartofSummer Undergraduate Research Fellowship
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dc.titleTo examine the combinatorial therapeutic effects of EGFR inhibitor and mTORC2 inhibitor for treatment of pancreatic cancer


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