Hybrid gene therapy designed to fully understand the underlying molecular cancer process may be a feasible option

Abstract

Combination gene therapy properly tailored to a full understanding of the underlying molecular cancer process may be a possible approach. In developing malignancies, the uptake and concentration of tumor suppressors at their target locations may be controlled. As with p53, this intracellular compartmentalization can be done by modulating target gene nuclear transport via imports and exports. Mediating PTMs such as ubiquitin, phosphorylation, and dephosphorylation to impact protein location is also a feasible method. For example, proteasome inhibitors directly or indirectly enhance nuclear localization of proteasome-target proteins such MG-132 and Lactacystin in acute myeloid leukemia PTM regulation is also crucial for managing protein stability; decreased ubiquitination by NEDD8 inhibitors boosts protein stability, which improves mitochondrial localization, although COX-2 inhibitors promote p53 stability and nuclear localisation. PTMs also play a crucial function in binding DNA control. For example, N-terminal phosphorylation and other PTMs alter p53's DNA-binding affinity and selectivity. A careful balance of gene therapy, transport inhibitors, kinase inhibitors, and post-translational modification inhibitors might be a potential alternative. In combined therapy, the p53 nuclear protein displays synergistic activation by enhancing actinomycin-D kinase and inhibiting upregulated-MDM2 from binding through nutlin-3a to p53. Using PEST-NPs as gene treatments requires a pragmatic approach due to their heterogeneous cancer activity.