RT Journal Article
ID 320db83e0fe2d1a2
A1 Safa, Ahmad R.
T1 Resistance to Cell Death and Its Modulation in Cancer Stem Cells
JF Critical Reviews™ in Oncogenesis
JO CRO
YR 2016
FD 2016-10-24
VO 21
IS 3-4
SP 203
OP 219
K1 cancer stem cells
K1 apoptosis resistance
K1 death receptors
K1 multidrug resistance
K1 Bcl-2 family
K1 c-FLIP
AB Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from
cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs. Several signaling pathways−including the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), maternal embryonic leucine zipper kinase (MELK), NOTCH1, and Wnt/Β-catenin&and expression of the CSC markers CD133, CD24, CD44, Oct4, Sox2, Nanog, and ALDH1A1 maintain CSC properties. Studying such pathways may help to understand CSC biology and lead to the development of potential therapeutic interventions to render CSCs more sensitive to cell death triggered by chemotherapy and radiation therapy. Moreover, recent demonstrations of dedifferentiation of differentiated cancer cells into CSC-like cells have created significant complexity in the CSCs hypothesis. Therefore, any successful therapeutic agent or combination of drugs for cancer therapy must eliminate not only CSCs but differentiated cancer cells and the entire bulk of tumor cells. This review article expands on the CSC
hypothesis and paradigm with respect to major signaling pathways and effectors that regulate CSC apoptosis resistance. Moreover, selective CSC apoptotic modulators and their therapeutic potential for making tumors more responsive to therapy are discussed. The use of novel therapies, including small-molecule inhibitors of specific proteins in signaling pathways that regulate stemness,
proliferation and migration of CSCs, immunotherapy, and noncoding microRNAs may provide better means of treating CSCs.

PB Begell House
LK https://www.dl.begellhouse.com/journals/439f422d0783386a,5c1116ad47548349,320db83e0fe2d1a2.html