Nanomedicine-Mediated Therapies to Target Breast Cancer Stem Cells

The study of CD44/CD24 and ALDH1 expression is the most accurate method to identify cancer stem cells (CSC) from breast cancer populations. However, the overlap between CD44(+)CD24(-/low) and ALDH1(high) CSC phenotypes in breast cancer seems to be very small, as well as their distribution among intrinsic breast cancer subtypes. Due to this discrepancy, it is imperative to improve the understanding of breast CSC marker distribution. 466 invasive breast carcinomas and eight breast cancer cell lines were analysed for the expression of CD44, CD24 and ALDH1, to evaluate their distribution among the distinct molecular subtypes. Basal-like tumours (76.5%) contained the higher percentage of cells with the CSC phenotype CD44(+)CD24(-/low) (p<0.0001). From ALDH1-positive cases, 39.4% were also basal-like tumours (p<0.0001). The analysis of breast cancer cell lines indicated that luminal cell lines are mainly enriched in a CD44(-/low)CD24(+) cell population, basal/mesenchymal breast cancer cell lines are enriched in the CD44(+)CD24(-/low) phenotype, whereas the remaining basal/epithelial cell lines are mainly positive for both markers. ALDH1 activity was mainly found in HER-OE and basal/epithelial breast cancer cell. CD44(+)CD24(-/low) and ALDH1(+) phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.

Breast cancer is not a single disease, but rather is composed of distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intratumoral diversity are the cancer stem cell and the clonal evolution hypotheses. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge.

A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed.