Investigate the Potential of Small Molecule Drug Candidates for the Inhibition of p53 Mutant Aggregation and Cancer Cell Proliferation

Abstract

The master’s thesis study focuses on the identification of novel small molecule drug candidates for inhibiting cancer causing p53 mutant peptide aggregation and tumor growth. p53 protein is a tumor suppressor protein, and controls cellular function and unwanted cell proliferation.When p53 is mutated it loses its function. Mutations of p53 are present in almost about 50-70% of all cancers. In a recent study, it has been reported that the p53 mutations cause aggregation and subsequent loss of p53 function, negative dominance and cell toxicity leading to advanced cancers. Further, p53 mutant aggregation has been observed in several cancers. Hence, there is growing interest in finding therapies for p53 mutant aggregation associated cancer. The objective of the thesis study include studying the inhibitory effect of small molecule drugs on p53 aggregation in vitro, their inhibitory potential on p53 mutant cancer cells proliferation in vitro, and finally an anoformulation of p53-antiaggregation drug candidates to treat p53 aggregation associated cancer with increased therapeutic efficacy. Characterization tools used for this study include biochemical assays, transmission electron microscopy, confocal microscopy, atomic force microscopy, dynamic light scattering, and cellular assays. The results of the thesis study show potential of small molecule drugs for treating cancer due to p53 aggregation.