PMID- 28779636
OWN - NLM
STAT- MEDLINE
DCOM- 20170919
LR  - 20220318
IS  - 1532-1967 (Electronic)
IS  - 0305-7372 (Linking)
VI  - 59
DP  - 2017 Sep
TI  - Phosphoinositide 3-kinase (PI3K) pathway inhibitors in solid tumors: From 
      laboratory to patients.
PG  - 93-101
LID - S0305-7372(17)30119-6 [pii]
LID - 10.1016/j.ctrv.2017.07.005 [doi]
AB  - The phosphoinositide 3-kinase (PI3K) pathway is an intracellular signaling 
      pathway that has regulatory roles in cell survival, proliferation, and 
      differentiation, and a critical role in tumorigenesis. In cancer, multiple 
      studies have investigated the therapeutic targeting of the PI3K pathway, and 
      multiple inhibitors targeting PI3K and its isoforms, protein kinase B/AKT, 
      mammalian target of rapamycin (mTOR), and other pathway proteins have been 
      developed. For the treatment of solid tumors, only allosteric mTOR inhibitors, 
      such as everolimus and temsirolimus, are currently approved for clinical use. 
      This review describes the PI3K inhibitors that have progressed from the 
      laboratory to late-stage clinical trials, and discusses the challenges that have 
      prevented other compounds from doing the same. Challenges to the therapeutic 
      effectiveness of some PI3K inhibitors include the absence of reliable and 
      effective biomarkers, their limited efficacy as single agents, insufficient 
      development of rational therapeutic combinations, the use of schedules with a 
      variety of off-target effects, and suboptimal therapeutic exposures. Therefore, 
      with regard to PI3K inhibitors currently in late-stage clinical trials, the 
      identification of appropriate biomarkers of efficacy and the development of 
      optimal combination regimens and dosing schedules are likely to be important for 
      graduation into clinical practice.
CI  - Copyright (c) 2017 The Author. Published by Elsevier Ltd.. All rights reserved.
FAU - Janku, Filip
AU  - Janku F
AD  - MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics 
      (Phase I Clinical Trials Program), Houston, TX, USA. Electronic address: 
      FJanku@mdanderson.org.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20170718
PL  - Netherlands
TA  - Cancer Treat Rev
JT  - Cancer treatment reviews
JID - 7502030
RN  - 0 (Protein Kinase Inhibitors)
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Clinical Trials, Phase II as Topic
MH  - *Drug Approval
MH  - Everolimus/therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Male
MH  - Molecular Targeted Therapy/*methods
MH  - Neoplasms/*drug therapy/mortality/pathology
MH  - Phosphatidylinositol 3-Kinases/drug effects/*genetics
MH  - Protein Kinase Inhibitors/pharmacology/*therapeutic use
MH  - Signal Transduction
MH  - Sirolimus/analogs & derivatives/therapeutic use
MH  - Survival Analysis
MH  - Treatment Outcome
MH  - United States
MH  - United States Food and Drug Administration
OTO - NOTNLM
OT  - Clinical trial
OT  - Inhibitors
OT  - Laboratory
OT  - Lessons
OT  - Phosphoinositide 3-kinase
OT  - Solid tumors
EDAT- 2017/08/06 06:00
MHDA- 2017/09/20 06:00
CRDT- 2017/08/06 06:00
PHST- 2017/04/11 00:00 [received]
PHST- 2017/07/11 00:00 [revised]
PHST- 2017/07/12 00:00 [accepted]
PHST- 2017/08/06 06:00 [pubmed]
PHST- 2017/09/20 06:00 [medline]
PHST- 2017/08/06 06:00 [entrez]
AID - S0305-7372(17)30119-6 [pii]
AID - 10.1016/j.ctrv.2017.07.005 [doi]
PST - ppublish
SO  - Cancer Treat Rev. 2017 Sep;59:93-101. doi: 10.1016/j.ctrv.2017.07.005. Epub 2017 
      Jul 18.