PMID- 27915972
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20220331
IS  - 0893-9675 (Print)
IS  - 0893-9675 (Linking)
VI  - 21
IP  - 3-4
DP  - 2016
TI  - Resistance to Cell Death and Its Modulation in Cancer Stem Cells.
PG  - 203-219
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/Beta-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.
FAU - Safa, Ahmad R
AU  - Safa AR
AD  - Indiana University Simon Cancer Center and Department of Pharmacology and 
      Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
LA  - eng
GR  - R01 CA080734/CA/NCI NIH HHS/United States
GR  - R01 CA090878/CA/NCI NIH HHS/United States
GR  - R01 CA101743/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Crit Rev Oncog
JT  - Critical reviews in oncogenesis
JID - 8914610
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Humans
MH  - Neoplasms/metabolism/*physiopathology
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - *Signal Transduction
PMC - PMC5356509
MID - NIHMS849559
EDAT- 2016/12/06 06:00
MHDA- 2017/10/03 06:00
PMCR- 2017/03/17
CRDT- 2016/12/06 06:00
PHST- 2016/12/06 06:00 [entrez]
PHST- 2016/12/06 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/03/17 00:00 [pmc-release]
AID - 5c1116ad47548349,320db83e0fe2d1a2 [pii]
AID - 10.1615/CritRevOncog.2016016976 [doi]
PST - ppublish
SO  - Crit Rev Oncog. 2016;21(3-4):203-219. doi: 10.1615/CritRevOncog.2016016976.