On 2014 May 27, G L Francis commented:

This editorial makes many pertinent points about the continuing frustration with the IGF-I Receptor as a cancer target for a number of therapeutic drugs of different classes directed at either the receptor extracellular domain or its intracellular tyrosine kinase domain. The only comment I wish to make on this excellent update of the field is a question in relation to the following statement “Although mutated IGF-IR has not been identified in any cancer, IGF-IR does appear to be up regulated in alveolar rhabdomyosarcoma, its signalling is required for survival of Ewing sarcoma cell lines, and the growth of osteosarcoma and desmoplastic small round cell turmors can be inhibited by IGF-IR blockade’’; and specifically, concerning the first part declaring the absence of any reports of receptor mutations in cancer.

This is not quite the case as a paper published earlier this year, Hum Pathol. 2014 Jun;45(6):1162-8. doi: 10.1016/j.humpath.2014.01.010. Epub 2014 Jan 31. ‘’Insulin-like growth factor 1 pathway mutations and protein expression in resected non-small cell lung cancer.’’ PMID: 24745618. http://www.ncbi.nlm.nih.gov/pubmed/24745618. wherein analysis of samples from 304 patients found a silent mutation in exon 16 and 3 mutations in introns of the IGF-I Receptor gene intracellular tyrosine kinase domain.

A further publication in Sarcoma. 2013;2013:450478. doi: 10.1155/2013/450478. Epub 2013 Jan 28 ‘’Insulin-like growth factor 1 receptor as a therapeutic target in ewing sarcoma: lack of consistent upregulation or recurrent mutation and a review of the clinical trial literature.”. http://www.ncbi.nlm.nih.gov/pubmed/23431249 in an analysis of 47 tumors identified only one mutation, a nonsynchronous change, R1353H, in a region with predicted low functional impact.

Moreover, these limited observations suggest that considerable work needs to be undertaken to redefine the approach to the IGF-I receptor as a therapeutic target – a point very well made by the author in this editorial statement.

On 2014 May 27, G L Francis commented:

This editorial makes many pertinent points about the continuing frustration with the IGF-I Receptor as a cancer target for a number of therapeutic drugs of different classes directed at either the receptor extracellular domain or its intracellular tyrosine kinase domain. The only comment I wish to make on this excellent update of the field is a question in relation to the following statement “Although mutated IGF-IR has not been identified in any cancer, IGF-IR does appear to be up regulated in alveolar rhabdomyosarcoma, its signalling is required for survival of Ewing sarcoma cell lines, and the growth of osteosarcoma and desmoplastic small round cell turmors can be inhibited by IGF-IR blockade’’; and specifically, concerning the first part declaring the absence of any reports of receptor mutations in cancer.

This is not quite the case as a paper published earlier this year, Hum Pathol. 2014 Jun;45(6):1162-8. doi: 10.1016/j.humpath.2014.01.010. Epub 2014 Jan 31. ‘’Insulin-like growth factor 1 pathway mutations and protein expression in resected non-small cell lung cancer.’’ PMID: 24745618. http://www.ncbi.nlm.nih.gov/pubmed/24745618. wherein analysis of samples from 304 patients found a silent mutation in exon 16 and 3 mutations in introns of the IGF-I Receptor gene intracellular tyrosine kinase domain.

A further publication in Sarcoma. 2013;2013:450478. doi: 10.1155/2013/450478. Epub 2013 Jan 28 ‘’Insulin-like growth factor 1 receptor as a therapeutic target in ewing sarcoma: lack of consistent upregulation or recurrent mutation and a review of the clinical trial literature.”. http://www.ncbi.nlm.nih.gov/pubmed/23431249 in an analysis of 47 tumors identified only one mutation, a nonsynchronous change, R1353H, in a region with predicted low functional impact.

Moreover, these limited observations suggest that considerable work needs to be undertaken to redefine the approach to the IGF-I receptor as a therapeutic target – a point very well made by the author in this editorial statement.