Phytochemicals in breast cancer therapy: decoding molecular pathways and pioneering therapeutic strategies

Background: Breast cancer constitutes a global health crisis, affecting millions worldwide and contributing significantly to cancer-related mortality. Its development, progression, and persistence are driven by complex molecular signaling networks, including the PI3K/Akt/mTOR, MAPK/ERK, NF-κB, TNF, and apoptotic pathways. Phytochemicals such as curcumin, genistein, resveratrol, and EGCG have demonstrated therapeutic potential by modulating these critical pathways, thereby inhibiting cancer cell proliferation, inducing apoptosis, suppressing metastasis, and potentially overcoming drug resistance, offering a promising basis for developing targeted and less toxic breast cancer therapies. Purpose: This review aims to examine the phytochemical composition of medicinal plants and elucidate the molecular pathways involved in their therapeutic effects against breast cancer. It also seeks to compile evidence from in vitro and in vivo studies, providing updated references for molecular targets suitable for phytochemical-based interventions. Methods: A comprehensive search of PubMed, Web of Science, ScienceDirect, and CNKI up to September 2024 used keywords on breast cancer, molecular pathways, natural active ingredients, and pharmacological activity. Eligible studies examined phytochemicals’ molecular mechanisms or therapeutic effects in breast cancer, while non-peer-reviewed, duplicate, or unrelated studies were excluded. Results: Decoding signaling pathways allows for the development of an individualized molecular profile for each patient, guiding the selection of optimal treatments while minimizing adverse effects. Assessing mutation status and protein expression within these pathways can help predict prognosis and evaluate therapeutic effectiveness. Phytochemicals, in particular, can inhibit cancer cell growth by targeting key signaling cascades that regulate the cell cycle, such as the PI3K/Akt and MAPK pathways. When used in combination with conventional therapies, these compounds may enhance treatment efficacy and reduce drug resistance. This review highlights the molecular pathways through which plant-derived phytochemicals act against breast cancer in both in vitro and in vivo settings, and elucidates their pharmacological effects at the molecular level. The findings provide a valuable reference for future research into molecularly targeted therapies and the development of breast cancer drugs from herbal sources.

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