Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 142, Issue 4, Pages 658-670Publisher
WILEY
DOI: 10.1002/ijc.31085
Keywords
breast cancer; natural phytochemicals; estrogen; obesity; chemoprevention; chemotherapeutics
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Funding
- Department of Defense [W81XWH-16-1-0641]
- Perricone Family Foundation, Los Angeles, CA
- Beckman Research Institute of City of Hope
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Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ER/ER ratio, upregulate proliferative pathways driven by ER and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/-catenin and NFB signaling along with regulating ER and ER, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.
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