Chemical Inductors of Proximity Associating DNA Damage-Binding Protein 2 and XIAP as Targeted Therapy for General Cancers

Abstract

While all cancers are classified as uncontrolled proliferations of cells, they manifest in many forms and may arise from a wide range of cellular anomalies. It has thus made finding a universal targeted cancer therapy a highly desirable goal. Several common biochemical changes associated with oncogenesis have been described in literature across all cancers, namely the Warburg effect (Heiden et al., 2009) (Warburg, 1925) and resistance to apoptosis (Hanahan & Weinburg, 2011). These hallmarks possess high potential to be used as targeting mechanisms in cancer treatment. Recent findings by Gourlsankar et al. have shown a promising new technique of linking the activity of a frequently activated cancer driver (B cell lymphoma 6) with an apoptosis promotor, allowing the creation of a synthetic biochemical pathway which rewires cancer driver activity to induce cell death, done through using a drug to covalently link two molecules that bond to each protein (Gourlsankar et al., 2023). While this approach specifically targeted diffuse large B cell lymphoma, it shows high promise for new strategies to approach eliminating cancer cells, namely in the artificial activation of tumor suppressor function through protein linkage and the consequent association in protein location within the cytosol. This paper aims to review the strategy of Gourlsankar et al., identifying ways to expand its concept towards generalized treatments using the hallmarks of cancer, and proposing a new theoretical drug mechanism using the linkage of DNA damage-binding protein 2 (DDB2) with X-linked inhibitor of apoptosis (XIAP) to induce cell death.