Curcumin: Modulator of Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer

SIMPLE SUMMARY: Breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide. It is a highly heterogeneous disease, classified according to hormone and growth factor receptor expression. Patients with triple negative breast cancer (TNBC) (estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor (HER2)-negative) and hormone-independent HER2 overexpressing subtypes still represent highly aggressive behavior, metastasis, poor prognosis, and drug resistance. Thus, new alternative anticancer agents based on the use of natural products have been receiving enormous attention. In this regard, curcumin is a promising lead in cancer drug discovery due its ability to modulate a diverse range of molecular targets and signaling pathways. The current review has emphasized the underlying mechanism of curcumin anticancer action mediated through the modulation of PI3K/Akt/mTOR, JAK/STAT, MAPK, NF-ĸB, p53, Wnt/β-catenin, apoptosis, and cell cycle pathways in hormone-independent breast cancer, providing frameworks for future studies and insights to improve its efficiency in clinical practice. ABSTRACT: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Despite the overall successes in breast cancer therapy, hormone-independent HER2 negative breast cancer, also known as triple negative breast cancer (TNBC), lacking estrogens and progesterone receptors and with an excessive expression of human epidermal growth factor receptor 2 (HER2), along with the hormone-independent HER2 positive subtype, still remain major challenges in breast cancer treatment. Due to their poor prognoses, aggressive phenotype, and highly metastasis features, new alternative therapies have become an urgent clinical need. One of the most noteworthy phytochemicals, curcumin, has attracted enormous attention as a promising drug candidate in breast cancer prevention and treatment due to its multi-targeting effect. Curcumin interrupts major stages of tumorigenesis including cell proliferation, survival, angiogenesis, and metastasis in hormone-independent breast cancer through the modulation of multiple signaling pathways. The current review has highlighted the anticancer activity of curcumin in hormone-independent breast cancer via focusing on its impact on key signaling pathways including the PI3K/Akt/mTOR pathway, JAK/STAT pathway, MAPK pathway, NF-ĸB pathway, p53 pathway, and Wnt/β-catenin, as well as apoptotic and cell cycle pathways. Besides, its therapeutic implications in clinical trials are here presented.