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Breast cancer (BC) is sub-categorized into several well-recognized subtypes including estrogen receptor (ER), progesterone receptor (PR), and HER2 triple-negative breast cancer (TNBC). It is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets such as the Wnt/β-catenin, STAT3, VEGF, EGFR, polyadenosine ribose polymerase inhibitors (PARPi) and DNA repair pathway, androgen pathway, and NOTCH pathway. Moreover, more research needs to be performed in the area of TNBC aiming at dissecting potential pathways and identifying potential molecular signatures to develop new targeted biologic modifiers. Natural agents are the abundant chemical compounds available from diverse plants. The authors aimed to summarize the current evidence and discuss the natural agents that target TNBC using different pathways.

Among the many types of breast cancer (BC), Triple-Negative Breast Cancer (TNBC) is the most alarming. It lacks receptors for the three main biomarkers: estrogen, progesterone, and human epidermal growth factor, hence the name TNBC. This makes its treatment a challenge. Surgical procedures and chemotherapy, performed either alone or in combination, seem to be the primary therapeutic possibilities; however, they are accompanied by severe complications. Currently, the formulation of drugs using natural products has been playing an important role in the pharmaceutical industries, owing to the drugs’ increased efficacies and significantly lessened side effects. Hence, treating TNBC with chemotherapeutic drugs developed using natural products such as flavonoids in the near future is much warranted. Flavonoids are metabolic compounds largely present in all plants, vegetables, and fruits, such as blueberries, onions, (which are widely used to make red wine,) chocolates, etc. Flavonoids are known to have enormous health benefits, such as anticancer, antiviral, anti-inflammatory, and antiallergic properties. They are known to arrest the cell cycle of the tumor cells and induces apoptosis by modulating Bcl-2, Bax, and Caspase activity. They show a considerable effect on cell proliferation and viability and angiogenesis. Various studies were performed at both the biochemical and molecular levels. The importance of flavonoids in cancer treatment and its methods of extraction and purification to date have been reported as individual publications. However, this review article explains the potentiality of flavonoids against TNBC in the preclinical levels and also emphasizes their molecular mechanism of action, along with a brief introduction to its methods of extraction, isolation, and purification in general, emphasizing the fact that its quantum of yield if enhanced and its possible synergistic effects with existing chemotherapeutics may pave the way for better anticancer agents of natural origin and significantly lessened side-effects.

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