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Access Type
WSU Access
Date of Award
January 2021
Degree Type
Thesis
Degree Name
M.S.
Department
Pharmaceutical Sciences
First Advisor
Dr. Arun K. Iyer
Abstract
TARGETED COMBINATION TREATMENT IN RENAL CELL CARCINOMA byAYATKSHI BARARI October 2021 Advisor: Dr. Arun K. Iyer Major: Pharmaceutical Sciences (Pharmaceutics) Degree: Master of Sciences Renal cell carcinoma (RCC) is a genitourinary cancer with high mortality and steadily rising incidence rate. RCC is a highly aggressive kidney tumor subtype, often showing resistance to conventional chemotherapy and radiotherapy. Development of drug resistance in RCC is attributed to many factors, such as active efflux pumps, genetic background, tumor hypoxic, altered cellular metabolism, and apoptosis impairment. Current treatment options include receptor tyrosine kinase inhibitors like cabozantinib (CB), mTOR inhibitors like everolimus, and hypoxia inducible factors 1 & 2 inhibitors like Belzutifan (BEL). The goal of this project is to screen effective combination therapy using Wayne State University developed apoptosis inducer CFM 4.16, with clinically used drugs - CB or BEL that inhibits the divergent tumor survival pathways and synergistically kills RCC better than monotherapy. Further research regarding encapsulating drug combination in RCC biomarker-selective nanoparticle to improve in vivo outcome and RCC selectivity with folic acid 66 (FA) for targeting folate receptor beta (FRb) and acetazolamide (ATZ) for targeting CA9 receptor of tumor hypoxia. Cytotoxic assay was performed to find synergistic drug combination followed by western blot analysis to study downregulation of tumorigenic protein and upregulation of pro- apoptosis protein. Our logical drug combination approach has significant potential to effectively kill RCC and downregulate crucial tumorigenic proteins. Further research and development of RCC biomarker selective nanoparticle as combination drug delivery vehicle has potential to overcome macrophage and hypoxia mediated drug resistance.
Recommended Citation
Barari, Ayatkshi, "Targeted Combination Treatment In Renal Cell Carcinoma" (2021). Wayne State University Theses. 847.
https://digitalcommons.wayne.edu/oa_theses/847