Abstract
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor-α progesterone receptor and human epidermal growth factor receptor-2. Treatment for this breast cancer subtype is restricted to multidrug chemotherapy and survival pathway-based molecularly targeted therapy. The long-term treatment options are associated with systemic toxicity, spontaneous and/or acquired tumor resistance and the emergence a of drug-resistant stem cell population. These limitations lead to advanced stage metastatic cancer. Current emphasis is on research directions that identify efficacious, naturally occurring agents representing an unmet need for testable therapeutic alternatives for therapy resistant breast cancer. Chinese herbs are widely used in traditional Chinese medicine in women for estrogen related health issues and also for integrative support for cancer treatment. This review discusses published evidence on a TNBC model for growth inhibitory effects of several mechanistically distinct nontoxic Chinese herbs, most of them nutritional in nature, and identifies susceptible pathways and potential molecular targets for their efficacy. Documented anti-proliferative and pro-apoptotic effects of these herbs are associated with downregulation of RB, RAS, PI3K, and AKT signaling, modulation of Bcl-2/BAX protein expressions and increased caspase activity. This review provides a proof of concept for Chinese herbs as testable alternatives for prevention/therapy of TNBC.
Highlights
Progression of breast cancer to advanced stage metastatic disease represents a major cause of mortality in women
triple-negative breast cancer (TNBC) lacks the expressions of estrogen receptor-α (ER-α), progesterone receptor (PR) and of amplified human epidermal growth factor recptor-2 (HER-2), and is at high risk for developing chemo-resistance and distant metastasis [3]
TNBC exhibits aberrant signaling of the tumor suppressor RB gene, and activation of rat sarcoma (RAS), phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT) signaling pathways that facilitate hyper-proliferation, increased migration/invasion and subsequent survival of cancer cells [4]
Summary
Progression of breast cancer to advanced stage metastatic disease represents a major cause of mortality in women. TNBC are frequently associated with systemic toxicity, spontaneous or acquired tumor resistance and emergence of a therapy resistant cancer stem cell population, all of which favor progression of therapy resistant disease [6] These limitations of long-term therapeutic options emphasize investigations that focus on identification of efficacious non-toxic agents that display distinct specificity and selectivity for cancer cells. Many of them nutritional in nature, have been traditionally used for the management of general health concerns and for women’s estrogen health issues, including breast diseases These herbs lack clinical systemic toxicity, and because of their nontoxic nature and documented human use [17,18,19,20], may represent testable alternatives for secondary prevention/therapy of TNBC. These research directions have provided mechanistic leads to suggest that Chinese herbs may represent nontoxic testable alternatives for secondary prevention/therapy of TNBC
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