Novel Treatment of Breast and Prostate Cancer, and Mesothelioma by Targeting Cancer Stem Cells

Abstract

Cancer is a major cause of death in the western world and is becoming an increasing world-wide problem. Even though treatment and therapeutic approaches to cancer have become better and there has been great improvement in the diagnosis of this group of pathologies, many cancer types are still lethal as there is no substantial treatment available. Further, even if treatment is successful, there is a significant risk of tumour recurrence, and such a tumour is then even harder to treat due to the acquired resistance in response to exposure to the initial treatment used. Cancer stem cells (CSCs) have been suggested as a reason behind more resistant tumours and tumour recurrence. Hence, CSCs are emerging as an important target for chemotherapy in order to suppress the re-initiation of tumours. The work of this laboratory has focused on two mitocans (mitochondrially-targeted anti-cancer compounds), α-tocopheryl succinate and its mitochondrially targeted derivative MitoVES. These anti-cancer agents have been shown to be effective against a variety of cancer cells and several in vivo mouse models of cancer, while being non-toxic to normal tissue. Whether they are able to target CSCs was one of the main aims of this study. This thesis addresses several questions in regards to CSCs. Firstly, breast and prostate cancer cell lines (MCF7 and LNCaP, respectively) and a mesothelioma cell line (IstMes2) as well as primary glioblastoma cells grown in the form of spheres were confirmed as a valid model to study CSC biology and resistance to apoptosis, as both phenotypical and genotypical features confirmed increased levels of stemness.