Examining the effects of anti-cancer combination therapy on tumor cell proliferation, migration and chemoresistance: Targeting Autophagy and Other Novel Pathways.

Abstract

Autophagy is a cellular catabolic which is known to be activated by cellular stress and acts as a critical cell survival pathway. Solid tumours experience different microenvironmental metabolic stresses such as hypoxia and nutrient/energy deprivation. These highly stressful microenvironmental conditions could lead to activation of the pro-survival autophagic pathway, leading to cancer progression. Currently, clinically available autophagy inhibitors (e.g., chloroquine) only provides modest inhibitory activity. Hence, development of novel strategies to potently inhibit the autophagic pathway are warranted. This thesis explores the effect of anti-cancer combination therapy ,via targeting autophagy with specific autophagy inhibitors directed toward major molecules in the autophagic pathway and other novel pathways, on tumour cell proliferation, migration and chemoresistance.