Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Abstract

Drug resistance is one of the main challenges in cancer therapy, including in the treatment of female-specific malignancies, which account for more than 60% of cancer cases among women. Therefore, elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches. Notably, Notch signaling, including either receptors or ligands, has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer. Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts, several studies focused on the Notchdependent regulation of the cancer stem cell (CSC) subpopulation or the induction of the epithelial-tomesenchymal transition (EMT), both features implicated in either intrinsic or acquired resistance. Indeed, the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSCdriven drug resistance. Moreover, other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment. Collectively, there is a long way to go before every facet will be fully understood; nevertheless, some small pieces are falling neatly into place. Overall, the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.

The Role of miR-92b-3p in Notch Signaling and Monitoring of Oral Squamous Cell Carcinoma

“…It is widely known that the Notch signaling pathway is closely associated with stem cell properties and chemotherapy resistance [13,14]. We observed that miR-92b-3p upregulated OSCC cells exhibited greater resistance, with a 2.41-fold higher IC50 for cisplatin than that of control cells (Fig.…”

Navigating breast cancer complexity: Deciphering the cross talk of Wnt/β catenin and Notch pathways in development and diseases

“…Conversely, when Notch signaling is ectopically activated, it leads to an increased rate of cell proliferation. These observations highlight the potential therapeutic value of targeting Notch signaling in breast tumor treatment to curb excessive cell proliferation and impede tumor growth 120 .…”

Juglone Inhibits Tumor Metastasis by Regulating Stemness Characteristics and the Epithelial-to-Mesenchymal Transition in Cancer Cells both in Vitro and in Vivo

“…Traditional treatments used to prevent tumor metastasis and recurrence, including radiotherapy and chemotherapy, kill tumor cells by interfering with DNA replication or cell cycle advance [5,23]. However, due to their feature of inactive or very slow proliferation, CSCs can successfully escape radiotherapy and chemotherapy and play an important role in maintaining minimal residual disease which may result in metastatic tumor formation [24]. It is widely accepted that targeting CSCs may provide a promising therapeutic approach to reduce the risk of cancer recurrence and metastasis [25].…”