The contribution of insulin-like
growth factors (IGFs) to cancer biology has been extensively studied in cell
lines, revealing that IGFs activate type 1 IGF receptors (IGF-1Rs) to promote
cell cycle progression, cell survival, motility and invasion. These findings
provoked interest in studying IGF-1R expression in clinical cancers, and in
development of drugs that block IGF signaling.
However, there has been striking variation in
reported IGF-1R expression in tumors and normal tissues when detected by
immunohistochemistry. For example IGF-1R was reported to be unchanged or down -regulated
in prostate cancer compared with benign prostate, although since our report
of IGF-1R up-regulation at the mRNA and protein level most publications support
up-regulation.
This lack of consensus also
confounds attempts to interpret results of clinical trials of novel IGF
inhibitory drugs. Early trials reported striking clinical responses to IGF-1R
inhibition but later trials showed very limited activity in unselected
patients. This raises the question as to whether tumor IGF-1R expression
correlates with sensitivity to IGF-1R inhibition. Preclinical reports
supporting such a link include studies in non-small cell lung cancer.
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