Synergistic modulation of p53-HMGB1 complex and its binding to DNA: The role of nanotechnology in overcoming cancer drug resistance; A literature review and in-silico analysis.

The interplay between the tumor suppressor protein p53 and high mobility group box 1 (HMGB1) is critical in cancer therapy, influencing responses to chemotherapy, radiotherapy, and immunotherapy. Despite the significance of these interactions, the relationship between these factors in treatment remains inadequately explored, underscoring the urgent need for further investigation. Hence, this review elucidates the mechanisms by which p53 and HMGB1 modulate cellular stress responses, apoptosis, and autophagy, highlighting their roles in multidrug resistance (MDR). Additionally, we conducted an in-silico study on the structure of the p53 protein, p53-DNA complex, the p53-HMGB1 complex, as well as the impact of their mutations within the p53-HMGB1-DNA binding dynamics. Recent advancements in nanotechnology offer promising strategies for enhancing therapeutic efficacy through targeted delivery systems that simultaneously modulate p53 and HMGB1 pathways. By integrating these molecular insights with nanotechnology, we propose a synergistic approach to overcoming treatment resistance and improving patient outcomes.