Drug-resistant Stem Cell Models for the Hormone-responsive Luminal A Breast Cancer

Abstract

Background: Progression of early stage breast cancer to advanced stage metastatic disease represents a major cause of death in women. The Luminal A breast cancer subtype exhibits acceptable response to Chemo-endocrine and targeted therapy. However, these treatment options are associated with intrinsic/acquired therapy resistance and emergence chemo-resistant cancer initiating stem cell population, and resultant progression to advanced stage metastatic disease. These limitations emphasize an unmet need for the development of reliable models for cancer stem cells that facilitate identification of efficacious therapeutic alternatives. Documented human consumption, low systemic toxicity, preclinical cancer growth inhibitory efficacy and stem cell targeting efficacy of natural products, such as dietary phytochemicals and nutritional herbs, provide mechanistic leads for these agents as testable therapeutic alternatives. Objectives: The objectives of the present review are to i.) Provide a systematic discussion of published evidence relevant conceptual background of conventional/targeted therapy and nutritional herbs as testable alternatives, ii.) Growth inhibitory efficacy of nutritional herbs in a cellular model for the Luminal A breast cancer, iii.) Breast cancer stem cell biology and stem cell models for therapy-resistant breast cancer, and iv.) Future research directions. Conclusions: Collectively, all the elements discussed in the present review validate mechanism-based experimental approaches to identify and prioritize potential therapeutic alternatives. Future Research: This review provides a rationale for investigations on patient-derived tumor samples that may minimize extrapolation of the preclinical data for their clinical relevance and translatability.