PMID- 18927274
OWN - NLM
STAT- MEDLINE
DCOM- 20081216
LR  - 20220129
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 20
DP  - 2008 Oct 15
TI  - The type 1 insulin-like growth factor receptor pathway.
PG  - 6364-70
LID - 10.1158/1078-0432.CCR-07-4879 [doi]
AB  - Research conducted over the past two decades has shown the importance of the type 
      1 insulin-like growth factor receptor (IGF1R) in tumorigenesis, metastasis, and 
      resistance to existing forms of cancer therapy. The IGF1R itself has only 
      recently been accepted as a credible treatment target, however, perhaps 
      reflecting the potential problems for drug design posed by normal tissue IGF1R 
      expression, and close homology with the insulin receptor. Currently approximately 
      12 anti-IGF1R therapeutics are undergoing clinical evaluation, including blocking 
      antibodies and tyrosine kinase inhibitors. This review will summarize the 
      principal signaling pathways activated by IGF1R and the preclinical data that 
      validated this receptor as a treatment target. We will review clinical progress 
      in the testing of IGF1R inhibitory drug candidates, the relative benefits and 
      potential toxicities of coinhibition of the insulin receptor, and the rationale 
      for combining IGF1R blockade with other cancer treatments. An understanding of 
      IGF1R signaling is important because it will guide the incorporation of 
      appropriate molecular markers into clinical trial design. This will be key to the 
      identification of patients most likely to benefit, and so will influence the 
      ability of IGF1R inhibition to make the transition from experimental intervention 
      to clinical therapy.
FAU - Chitnis, Meenali M
AU  - Chitnis MM
AD  - Department of Medical Oncology, Churchill Hospital, Oxford, UK.
FAU - Yuen, John S P
AU  - Yuen JS
FAU - Protheroe, Andrew S
AU  - Protheroe AS
FAU - Pollak, Michael
AU  - Pollak M
FAU - Macaulay, Valentine M
AU  - Macaulay VM
LA  - eng
GR  - G0601061/MRC_/Medical Research Council/United Kingdom
GR  - CRUK_/Cancer Research UK/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/therapeutic use
MH  - Humans
MH  - Neoplasms/drug therapy
MH  - Receptor, IGF Type 1/antagonists & inhibitors/*physiology
MH  - Receptor, Insulin/physiology
MH  - Signal Transduction/drug effects
RF  - 71
EDAT- 2008/10/18 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/10/18 09:00
PHST- 2008/10/18 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/18 09:00 [entrez]
AID - 14/20/6364 [pii]
AID - 10.1158/1078-0432.CCR-07-4879 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Oct 15;14(20):6364-70. doi: 10.1158/1078-0432.CCR-07-4879.