Abstract
Background: The treatment options for breast cancer are dependent on the expression status of hormones and growth factor receptors. Hormone receptor positive Luminal A and Luminal B breast cancer subtypes exhibit favorable response to targeted endocrine therapy and/or human epidermal receptor-2 (HER-2) HER-2 therapy respectively. Hormone receptor negative, HER positive HER-2-enriched subtypes respond only to HER-2 targeted therapy. Hormone receptor negative and HER-2 negative triple negative (TNBC) subtypes respond only to conventional cytotoxic chemotherapy, and are notable for the presence of putative stem cell population. These subtype selective treatment options are universally associated with phenotypic therapy resistance, leading to emergence of chemo-resistant cancer initiating stem cell population that is responsible for initiation, progression and recurrence of therapy-resistant breast cancer. These limitations emphasize development of reliable drug-resistant cancer stem cell model for TNBC and identification of novel testable alternatives with stem cell selective efficacy.
Objectives: The present review article provides an overview of published evidence for i) Molecular characterization of TNBC subtype, ii) Limitations relevant to mainstream treatment options and advantages of natural products as testable therapeutic alternatives, and iii) Development and characterization of reliable drug-resistant TNBC stem cell model.
Conclusion: Published evidence discusses relevant information regarding molecular classification of TNBC subtype, significance of natural products as testable alternatives for TNBC subtype and applicability of drug-resistant stem cell model to investigate stem cell targeting efficacy of natural products.
Future Research: Collectively, discussed evidence defines a scientifically robust rationale to undertake future investigations on patient derived tumor explants and patient derived tumor organoids as a valuable strategy to reduce extrapolation of preclinical data for their clinical relevance and translatability for cancer stem cell targeting efficacy of natural products on breast cancer.