Melittin-Based Therapeutic Strategies Targeting Tumor Microenvironment in Breast Cancer: A Systematic Literature Review

Abstract

Background: Breast cancer remains one of the leading causes of cancer mortality worldwide. The tumor microenvironment (TME) plays a crucial role in cancer progression, metastasis, and therapeutic resistance. Melittin, a bioactive peptide derived from bee venom, has demonstrated promising anticancer properties through multiple mechanisms including apoptosis induction, inhibition of angiogenesis, and immune modulation. Objective: This systematic review aims to analyze current evidence regarding the anticancer mechanisms of melittin and its delivery strategies targeting tumor microenvironment in breast cancer. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Articles were identified through PubMed database searches using keywords related to melittin and cancer therapy. Studies published between 2021 and 2026 investigating melittin-based therapeutic approaches were included. Data extracted included study design, intervention type, molecular targets, and therapeutic outcomes. Results: Six studies met the inclusion criteria. Melittin demonstrated significant anticancer activity through suppression of HIF-1α signaling, induction of apoptosis, modulation of immune response, and remodeling of tumor microenvironment. Advanced drug delivery technologies such as nanocarriers, liposomes, and peptide-based systems significantly improved therapeutic targeting and reduced toxicity. Conclusion: Melittin represents a promising bioactive compound for breast cancer therapy, particularly when combined with advanced delivery systems targeting tumor microenvironment. Future research should focus on clinical trials to evaluate safety and therapeutic efficacy in humans