Targeting Notch signalling pathway of cancer stem cells

Abstract

Cancer stem cells (CSCs) have been defined as cells within tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. CSCs have been increasingly identified in blood cancer, prostate, ovarian, lung, melanoma, pancreatic, colon, brain and many more malignancies. CSCs have slow growth rate and are resistant to chemotherapy and radiotherapy that lead to the failure of traditional current therapy. Eradicating the CSCs and recurrence, is promising aspect for the cure of cancer. The CSCs like any other stem cells activate the signal transduction pathways that involve the development and tissue homeostasis, which include Notch signaling pathway. The new treatment targets these pathway that control stem-cell replication, survival and differentiation that are under development. Notch inhibitors either single or in combination with chemotherapy drugs have been developed to treat cancer and its recurrence. This approach of targeting signaling pathway of CSCs represents a promising future direction for the therapeutic strategy to cure cancer.

Honokiol: A Review of Its Anticancer Potential and Mechanisms

“…Notch signalling has been implicated in maintaining tissue homeostasis, including the regulation of self-renewal in adult stem cells, organ development, and embryonic development [200][201][202]. In mammals, the Notch receptor family comprises of four receptors (Notch-1, Notch-2, Notch-3, and Notch-4) and five ligands (Delta-like-1, Delta-like-3, Delta-like-4, Jagged-1, and Jagged-2).…”

“…The Notch pathway plays a complex role in the tumourigenesis of both hematologic and solid tissues. In fact, Notch signalling plays a vital role in regulating cellular differentiation, angiogenesis, proliferation, and apoptosis [201].…”

The Application of Biomaterials in the Treatment of Platinum‐Resistant Ovarian Cancer

“…CSC‐LCs function rely on their ability to promote the activity of stemness pathways. The genes involved in these pathways are often dysregulated in Oca CSC‐LCs, and are usually integrated into three main clusters involving the WNT/ Β‐ CATENIN/NOTCH network, the MEK/MAPK network and the NANOG/SOX2/OCT4/KLF4 network . Interestingly, in Oca patients with platinum‐resistant tumors, these three pathways were found to be interconnected through a fourth pathway involving C‐KIT, STAT3, NOTCH1 and MYC .…”

“…The genes involved in these pathways are often dysregulated in Oca CSC-LCs, and are usually integrated into three main clusters involving the WNT/B-CATENIN/NOTCH network, the MEK/ MAPK network and the NANOG/SOX2/OCT4/KLF4 network. [32,33] Interestingly,i nO ca patients with platinum-resistant tumors, these three pathways were found to be interconnected through af ourth pathway involving C-KIT,S TAT3, NOTCH1 and MYC. [32] This evidence for C-KIT cross-talk with NANOG and OCT4 specifically,issupported by earlier studies which revealed that cisplatin treatment enhances the expression of C-KIT, NANOG and OCT4 in residual ovarian cancerc ells in vitro.…”

Single cell derived organoids capture the self-renewing subpopulations of metastatic ovarian cancer

“…This is consistent with previous observations showing that abnormal expression levels and mutations of genes involved in the cholesterol homeostasis and lipid metabolism are related to cancer 37,38 and OC 39,40 . Likewise, Notch signaling that regulates cell proliferation, stem cell maintenance and that plays a critical role in the cross talk between angiogenesis and CICs self renewal was also an enriched pathway defining the similarity between fresh and scOCOs cells 41 ( fig. 5c).…”