Possible Applications of Azurin, a Copper-Containing Protein, in Cancer Treatment: Prospects and Challenges

Conventional cancer therapies are limited by systemic toxicity, poor selectivity, and drug resistance. Bacterial proteins, such as azurin, represent a promising alternative due to their tumor selectivity, low immunogenicity, and multifunctional mechanisms. This review highlights recent progress in azurin-based anticancer strategies, including mechanisms of action, structural modifications, and integration with peptide systems, nanotechnology, and gene therapy.

A search for articles using the keywords "azurin, cancer" was conducted on the Google Scholar and PubMed databases, with an emphasis on the years 2023-2024.

Azurin and its peptide derivative p28 selectively target cancer cells by stabilizing p53, inducing apoptosis, and arresting the cell cycle, while also modulating key signaling pathways. Structural features of azurin enable interactions with multiple molecular targets, and p28 enhances cellular uptake and sensitizes tumors to chemotherapeutics. Advanced delivery platforms, including engineered bacteria (E. coli Nissle 1917, S. typhimurium VNP-20009), chimeric peptides, and nanocarriers, improve tumor targeting and therapeutic outcomes. Preclinical models and clinical trials demonstrate low toxicity and efficacy against various solid tumors and gliomas.

Evidence supports azurin as a versatile anticancer agent with unique advantages over conventional therapies. Its compatibility with delivery innovations enhances precision and minimizes systemic toxicity. However, further optimization, large-scale clinical validation, and long-term safety studies are required.

Azurin and its derivatives provide a promising platform for anticancer therapy, offering tumor specificity, low toxicity, and synergy with multiple treatment modalities. Their integration into advanced delivery and genetic systems may significantly improve cancer treatment and recurrence prevention.