PMID- 35987481
OWN - NLM
STAT- MEDLINE
DCOM- 20220913
LR  - 20220914
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 183
DP  - 2022 Sep
TI  - Targeting Akt/PKB in pediatric tumors: A review from preclinical to clinical 
      trials.
PG  - 106403
LID - S1043-6618(22)00348-6 [pii]
LID - 10.1016/j.phrs.2022.106403 [doi]
AB  - The serine/threonine kinase Akt is a major player in the phosphoinositide 
      3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway, and 
      its modulation impacts multiple cellular processes such as growth, proliferation, 
      and survival. Several abnormalities in this pathway have been documented over the 
      years, and these alterations were shown to have great implications in 
      tumorigenesis and resistance to chemotherapy. Thus, multiple Akt inhibitors have 
      been developed and tested in adult tumors, and some of them are currently 
      undergoing phase I, II, and III clinical trials for distinct cancers that arise 
      during adulthood. Despite that, the impact of these inhibitors is still not fully 
      understood in pediatric tumors, and Akt-specific targeting seems to be a 
      promising approach to treat children affected by cancers. This review summarizes 
      recent available evidence of Akt inhibitors in pediatric cancers, from both 
      preclinical and clinical studies. In short, we demonstrate the impact that Akt 
      inhibition provides in tumorigenesis, and we suggest targeting the PI3K/Akt/mTOR 
      signaling pathway, alone or in combination with other inhibitors, is a feasible 
      tool to achieve better outcomes in pediatric tumors.
CI  - Copyright (c) 2022 Elsevier Ltd. All rights reserved.
FAU - Toson, Bruno
AU  - Toson B
AD  - Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical 
      Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 
      Brazil.
FAU - Fortes, Isadora S
AU  - Fortes IS
AD  - Pharmaceutical Synthesis Group (PHARSG), College of Pharmacy, Federal University 
      of Rio Grande do Sul, Porto Alegre, RS, Brazil; Pharmaceutical Sciences Graduate 
      Program, Federal University of Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 
      Porto Alegre, RS 90610-000, Brazil.
FAU - Roesler, Rafael
AU  - Roesler R
AD  - Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical 
      Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 
      Brazil; Department of Pharmacology, Institute for Basic Health Sciences, Federal 
      University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
FAU - Andrade, Saulo F
AU  - Andrade SF
AD  - Pharmaceutical Synthesis Group (PHARSG), College of Pharmacy, Federal University 
      of Rio Grande do Sul, Porto Alegre, RS, Brazil; Pharmaceutical Sciences Graduate 
      Program, Federal University of Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, 
      Porto Alegre, RS 90610-000, Brazil. Electronic address: saulo.fernandes@ufrgs.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20220818
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Carcinogenesis
MH  - Child
MH  - Humans
MH  - *Neoplasms/drug therapy
MH  - *Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - AZD5363 (PubChem CID 25227436)
OT  - Akt inhibitor
OT  - CCT128930 (PubChem CID17751819)
OT  - GDC-0068 (PubChem CID 24788740)
OT  - GSK2110183 (PubChem CID 92044396)
OT  - GSK2141795 (PubChem CID 51042438)
OT  - GSK690693 (PubChem CID 16725726)
OT  - MK-2206 (PubChem CID 24964624)
OT  - PI3K/Akt/mTOR pathway
OT  - Pediatric cancer
OT  - Perifosine (PubChem CID 148177)
OT  - TAS-117 (PubChem CID 66555816)
OT  - Targeted therapy
OT  - Triciribine (PubChem CID 65399)
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/08/21 06:00
MHDA- 2022/09/14 06:00
CRDT- 2022/08/20 19:35
PHST- 2022/06/28 00:00 [received]
PHST- 2022/08/01 00:00 [revised]
PHST- 2022/08/15 00:00 [accepted]
PHST- 2022/08/21 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/08/20 19:35 [entrez]
AID - S1043-6618(22)00348-6 [pii]
AID - 10.1016/j.phrs.2022.106403 [doi]
PST - ppublish
SO  - Pharmacol Res. 2022 Sep;183:106403. doi: 10.1016/j.phrs.2022.106403. Epub 2022 
      Aug 18.