Targeting triple negative breast cancer stem cells using nanocarriers

Abstract

Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, and treatment responses. Categorization of subtypes is based on the presence or absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), leading to subtypes such as luminal A, luminal B, HER2-positive, and triple-negative breast cancer (TNBC). TNBC, comprising around 20% of all breast cancers, lacks expression of ER, PR, and HER2 receptors, rendering it unresponsive to targeted therapies and presenting significant challenges in treatment. TNBC is associated with aggressive behavior, high rates of recurrence, and resistance to chemotherapy. Tumor initiation, progression, and treatment resistance in TNBC are attributed to breast cancer stem cells (BCSCs), which possess self-renewal, differentiation, and tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), and immune modulation (cytokines, immune checkpoint inhibitors) are among the key targets discussed in this review. However, targeting the BCSC subpopulation in TNBC presents challenges, including off-target effects, low solubility, and bioavailability of anti-BCSC agents. Nanoparticle-based therapies offer a promising approach to target various molecular pathways and cellular processes implicated in survival of BSCS in TNBC. In this review, we explore various nanocarrier-based approaches for targeting BCSCs in TNBC, aiming to overcome these challenges and improve treatment outcomes for TNBC patients. These nanoparticle-based therapeutic strategies hold promise for addressing the therapeutic gap in TNBC treatment by delivering targeted therapies to BCSCs while minimizing systemic toxicity and enhancing treatment efficacy.

Keywords: Anti-BSCS agents; Breast cancer stem cells; Molecular targets; Nano carriers.

Fig. 1

The role of cancer stem cells in Tumour recurrence & Transmission. A Conventional therapy for elimination of non-tumour stem cells & stem cells and results in tumour relapse; B The activation of transcription factors, for epithelial-to-mesenchymal transition (EMT), in BCSCs or metastatic cells. This phenotypic change facilitates their dissemination and migration. Cells undergoing EMT acquire the ability to enter the bloodstream, evading immune surveillance, and eventually reach target organs. Once in the specific organ site, these cells can enter a Inactive state that can last for months to decades. Alternatively, they can endure mesenchymal-to-epithelial transition (MET), reverting back to an epithelial state, and initiate the growth of secondary tumors. C Essential Signaling Pathways Associated with the Survival of BCSCs [14]

Fig. 2

Therapies Against TNBC