Targeting Drug Metabolism for Triple Negative Breast Cancer: A Systematic Review

INTRODUCTION: The global rise in breast cancer incidence and associated mortality remains a pressing public health concern. Despite advancements in diagnostic modalities and the availability of diverse therapeutic strategies, mortality rates continue to escalate, particularly in aggressive subtypes, such as triple-negative breast cancer (TNBC). MATERIALS AND METHODS: A thorough systematic review of literature relevant to the theme of this article was conducted using PubMed, Google Scholar, ScienceDirect, and other databases, applying a six-year filter. Figures related to breast cancer prevalence were obtained from the webpage of the Global Cancer Observatory. RESULTS: Strategic modulation of metabolic circuits holds promise for reversing resistance phenotypes. Drug-metabolizing enzymes represent a compelling therapeutic target due to their diverse isoforms and broad substrate specificity in xenobiotic metabolism. Employing selective inducers or inhibitors of these enzymes may enhance drug bioavailability and potentiate complete pathological responses. DISCUSSION: This systematic review examines targeted approaches to managing TNBC by modulating metabolic pathways and drug-metabolizing enzymes. These enzymes and pathways exhibit differential expression patterns across cancer subtypes, often driving resistance mechanisms. Furthermore, emerging challenges and evolving trends in TNBC therapy and drug development are addressed, emphasizing the need for precision-targeted interventions to tackle the unique metabolic landscape of resistant tumors. CONCLUSION: Overcoming drug resistance is critical for enhancing chemotherapeutic outcomes and minimizing systemic toxicity associated with high-dose regimens. Targeting metabolic pathways involved in breast cancer progression, as well as drug-metabolizing enzymes, can be a vital strategy to circumvent drug resistance in both hormone receptor-positive and hormone receptor-negative breast cancers.