Haarith Ndiaye

Title: Sensitising liver cancer cells to apoptosis through targeted inhibition of fatty acid activation

Summary:

Since studying cancer in my second year of medicine, I have been captivated by the intricate genetic and biochemical mechanisms by which malignancies subvert normal cellular and molecular biology. Thus, when the prospect of a research project on the topic of liver cancer arose I was keen to pursue it. Liver cancer is of particular interest to me as it is a rapidly rising cause of cancer-related mortality and a better understanding of the disease, especially at cellular and molecular levels, is required in order to developed more effective therapeutic agents.

Two enzymes, ACSL3 and ACSL4, have been recently implicated in the progression and metastasis of cancer. However, their location in the cell remains undefined. Furthermore, one of these enzymes, ACSL4, has emerged as a critical mediator of a new form of cell death called ferroptosis. Linking these two themes together, this project focuses on understanding and targeting fatty acid activation in liver cancer cells as a novel strategy to treat liver cancer.

Further, understanding the regulatory mechanisms of these enzymes is of importance as dysregulation of long chain fatty acids has been associated with metabolic diseases such as NAFLD, a cause of HCC.

It is hoped that this research will provide proof of concept for a targeted, evidence-based approach for the selective induction of death in liver cancer cells. As these metabolic pathways preside in many other cancers, it is anticipated that these findings may very well be extended to encompass these too.