Targeting Key Molecular Mechanisms in Triple-Negative Breast Cancer Therapies with Natural Compounds

Area of Science:

• Oncology
• Pharmacology
• Natural Products Chemistry

Background:

• Triple-negative breast cancer (TNBC) lacks specific targets and effective therapies, presenting a significant clinical challenge.
• TNBC is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression, leading to aggressive behavior and poor prognosis.

Purpose of the Study:

• To review the therapeutic potential of natural compounds against TNBC.
• To investigate the mechanisms by which natural compounds target oncogenic pathways in TNBC.

Main Methods:

• A comprehensive literature search was performed using major scientific databases (PubMed, Scopus, Web of Science).
• Studies evaluating the anti-TNBC properties of natural compounds and their mechanisms of action were identified and analyzed.

Main Results:

• Several natural compounds (curcumin, resveratrol, quercetin, EGCG, berberine, thymoquinone) exhibit anticancer effects in TNBC models.
• These compounds inhibit proliferation, metastasis, and chemoresistance, and induce apoptosis by modulating pathways like PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, and Wnt/β-catenin.
• Natural compounds may enhance immunotherapy in BRCA-mutated TNBC when combined with PARP inhibitors, by affecting immune checkpoints like PD-L1.

Conclusions:

• Natural compounds offer a promising complementary approach for TNBC treatment by targeting key molecular pathways and overcoming resistance.
• Challenges including poor pharmacokinetics, limited bioavailability, and insufficient clinical validation require further investigation.
• Future research should prioritize combination therapies, nanodelivery systems, and biomarker-driven clinical trials for developing effective TNBC treatments.