The complex regulatory mechanisms of the BCL-2 family of proteins in cancer


Greaves, GJ (2019) The complex regulatory mechanisms of the BCL-2 family of proteins in cancer. PhD thesis, University of Liverpool.

[thumbnail of 201146324_Apr2019.pdf] Text
201146324_Apr2019.pdf - Unspecified
Download (7MB)

Abstract

Resistance to apoptosis is a key hallmark of most cancers. The BCL-2 family of proteins are the major arbiters of the cell death program and the interactions between pro- and anti-apoptotic members of this family are believed to shift the fate of a cell towards life or death. The anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL, MCL-1, BCL-w and BCL-2A1) are often overexpressed in cancer, thereby promoting abnormal cell survival. As a result, these proteins are highly attractive targets for novel chemotherapeutic approaches. The recent clinical success of inhibitors against BCL-2 (Navitoclax and Venetoclax) has launched the compounds known as BH3 mimetics into the chemotherapeutic spotlight and has led to the successful development of several highly potent MCL-1 inhibitors. The targeting of MCL-1 in cancer is critical to restoring sensitivity to other chemotherapeutic approaches, as MCL-1 is strongly associated with abnormal cell survival and chemoresistance in many cancers. The aims of this study were to (1) assess the specificity and potency of the novel MCL-1 inhibitor, S63845, as a single agent and in conjunction with other BH3 mimetics, to induce apoptosis in a range of cancer cell lines (2) characterise ... (continues)

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences > School of Medicine
Depositing User: Symplectic Admin
Date Deposited: 25 Jun 2019 15:36
Last Modified: 30 Sep 2024 02:15
DOI: 10.17638/03038636
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3038636
Altmetric
Share
CORE (COnnecting REpositories)