PMID- 19632946
OWN - NLM
STAT- MEDLINE
DCOM- 20100104
LR  - 20090727
IS  - 1938-0690 (Electronic)
IS  - 1525-7304 (Linking)
VI  - 10
IP  - 4
DP  - 2009 Jul
TI  - The rationale and development of therapeutic insulin-like growth factor axis 
      inhibition for lung and other cancers.
PG  - 262-72
LID - 10.3816/CLC.2009.n.037 [doi]
AB  - The insulin-like growth factor (IGF) axis involves elements of endocrine, 
      paracrine, and autocrine control. It is centrally involved in normal development 
      and growth. Core signaling is driven through the IGF-1 receptor (IGF-1R) in 
      either homo-multimeric complexes or hetero-multimeric complexes with the insulin 
      receptor (IR). Signaling is affected by a large number of upstream and downstream 
      factors, including the differential expression of various intracellular IR 
      substrates, a range of stimulatory ligands (insulin, IGF-1, and IGF-2), the 
      expression of specific clearance receptors (eg, IGF-2R), and different 
      IGF-binding proteins. Considerable evidence exists to implicate aspects of the 
      IGF axis in the development and maintenance of many different nonneoplastic and 
      neoplastic diseases, including both small-cell lung cancer and non-small-cell 
      lung cancer (NSCLC). A large number of different anticancer strategies directed 
      against the IGF axis are being developed. Monoclonal antibodies directed against 
      the IGF-1R are the furthest advanced clinically. Hyperglycemia appears to be a 
      class effect. To date, the major difference among the antibodies used in clinical 
      trials seems to be their plasma half-lives, leading to a number of different 
      administration regimens being taken forward. Early signals of monotherapy 
      activity have been notably reported in patients with Ewing sarcoma and in several 
      other cancers. Encouraging increases in the NSCLC response rate have already been 
      reported after the addition of an anti-IGF-1R antibody to first-line carboplatin 
      and paclitaxel. Explorations of aspects of ligands, binding proteins, receptors, 
      and receptor substrates are all ongoing to identify potential biomarkers 
      predictive of benefit from IGF axis intervention.
FAU - Camidge, D Ross
AU  - Camidge DR
AD  - Developmental Therapeutics Program, University of Colorado Cancer Center, Denver 
      Thoracic Oncology Program, University of Colorado Cancer Center, Denver, Colorado 
      80045, USA. ross.camidge@uchsc.edu
FAU - Dziadziuszko, Rafal
AU  - Dziadziuszko R
FAU - Hirsch, Fred R
AU  - Hirsch FR
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Lung Cancer
JT  - Clinical lung cancer
JID - 100893225
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Receptors, Somatomedin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Clinical Trials as Topic
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Proteins/genetics/metabolism
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Insulin-Like Growth Factor II/*metabolism
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Neoplasm Proteins/physiology
MH  - Rats
MH  - Receptors, Somatomedin/*metabolism
MH  - *Signal Transduction
RF  - 63
EDAT- 2009/07/28 09:00
MHDA- 2010/01/05 06:00
CRDT- 2009/07/28 09:00
PHST- 2009/07/28 09:00 [entrez]
PHST- 2009/07/28 09:00 [pubmed]
PHST- 2010/01/05 06:00 [medline]
AID - S1525-7304(11)70105-X [pii]
AID - 10.3816/CLC.2009.n.037 [doi]
PST - ppublish
SO  - Clin Lung Cancer. 2009 Jul;10(4):262-72. doi: 10.3816/CLC.2009.n.037.