Review Article Targeting BCL2-Proteins for the Treatment of Solid Tumours

permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Due to their central role in the regulation of apoptosis, the antiapoptotic BCL2-proteins are highly promising targets for the development of novel anticancer treatments. To this end, several strategies have been developed to inhibit BCL2, BCL-XL, BCL-w, and MCL1. While early clinical trials in haematological malignancies demonstrated exciting single-agent activity of BCL2-inhibitors, the response in solid tumours was limited, indicating that, in solid tumours, different strategies have to be developed in order to successfully treat patients with BCL2-inhibitors. In this review, the function of the different antiapoptotic BCL2-proteins and their role in solid tumours will be discussed. In addition, a comprehensive analysis of current small molecules targeting these antiapoptotic BCL2-proteins (e.g., ABT-737, ABT-263, ABT-199, TW-37, sabutoclax, obatoclax, and MIM1) will be provided including a discussion of the results of any clinical trials. This analysis will summarise the potential of BCL2-inhibitors for the treatment of solid tumours and will unravel novel approaches to utilise these inhibitors in clinical applications. 1. Mechanisms of Apoptosis Evasion of cell death or apoptosis is a key hallmark of cancer [1]. Generally, cells can die by apoptosis, a form of pro-grammed cell death, or after acute injury by necrosis and cell lysis, which initiates an inflammatory response. Apoptosi