Alternative therapeutics for oesophageal cancer : novel toxic bile acid derivatives to induce apoptosis and siRNA library screen to identify genes that regulate cell shape

Abstract

Oesophageal adenocarcinoma (OAC) is the sixth leading cause of cancer-related deaths worldwide, and has proven most challenging for surgeons as less than a third of patients are suitable for surgical resection due to advanced rate of disease or co-morbidities. Despite progress in surgical techniques and chemotherapy treatments, prognosis and median overall survival in patients with metastatic OAC remains poor and does not surpass 8-10 months. Failure of traditional therapy is a consequence of non-specific interactions and a high degree of toxicity and damage to normal cells. This necessitates the pursuit for more potent anti-cancer agents with less deleterious effects on the body. Several attempts have been made to utilize synthetically designed bile acid (BA)-based cytotoxic agents, however, only a relatively small number of compounds have been extensively characterized biochemically.