July 01, 2009
The complexity of cell signalling pathways in oncology
If we take a look at the IGF-1R pathway shown in the diagram, we can appreciate the sheer size and complexity of tyrosine kinase blocking downstream of the receptor.
One of the more recent trends that is showing up in clinical trials is to combine an mTOR inhibitor such as everolimus or temsirolimus, with an IGF-1R inhibitor such as NVP-AEW541 (Novartis) or IMC-A12 (ImClone), in solid tumours such as GIST and or liquid tumours such as lymphomas. The benefits of this strategy may outway the potential downsides, given the ubiquity of IGFR expression.
Another, similar, approach is to combine the mTOR with an EGFR or HER-2 inhibitor.
It remains to be seen whether receptor and downstreaming blocking will add any improvement in efficacy without introducing significant side effects, but intuitively, the approach makes sense and may even lead to a delay in disease progression or the development of resistance. Indeed, it is possible that patients may respond to different therapies, leading to the identification of new biomarkers for determining a more personalised approach to the treatment of cancer.
Time will tell.
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