Investigating Synergistic Abilities of Kinase Inhibitors and PTEN Protein for Combination Cancer Therapies
Fernandez, Thomas.
2017
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Abstract: A multitude of different drug modalities are used to treat cancer diagnoses in hopes of one day finding the silver bullet for cancer once and for all. Kinase inhibitors present as an interesting option for disease treatment in medical research as they specifically target, modulate, and control intracellular biological functions to impede disease mechanisms. Previously, our lab has devise... read mored a way of efficiently delivering recombinant PTEN protein using novel cationic lipid nanoparticles, which resulted in a means of selectively inhibiting PI3K phosphatase function within PTEN-deficient tumor cell lines. Building off this finding, we wanted to investigate whether or not this therapeutic modality could be expanded upon by finding synergistic relationships with various kinase inhibitors that target different nodes of the PI3K/Akt/mTOR pathway in efforts to boost the inhibitors' efficacy. After a series of in vitro delivery trials, significantly lowered cell viability against PTEN-deficient PC-3 cells was observed with the combination of recombinant PTEN protein and Temsirolimus, an mTOR inhibitor. This phenomenon can suggest a possible synergistic relationship between the two, which should be investigated further via protein immunoblotting methods amongst other techniques. Using combination therapy by dosing recombinant PTEN protein at a low cytotoxic concentration with kinase inhibitors could not only have an increased efficacy for cancer treatment in PTEN-deficient cells, but may also have a huge impact on patients' therapeutic experience through an overall reduction in drug dosage.
Thesis (M.S.)--Tufts University, 2017.
Submitted to the Dept. of Biomedical Engineering.
Advisor: Qiaobing Xu.
Committee: Xiaocheng Jiang, and James Van Deventer.
Keywords: Biomedical engineering, and Bioengineering.read less - ID:
- r781wt50v
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