A couple of new papers will be reviewed this week, thanks to everyone who sent in links and suggested topics for discussion. I'll try and cover one a day, although there were so many worthy of consideration! Please do keep the ideas coming, they are much appreciated.
For today, here's one I came across last week in one of the American Association of Cancer Research (AACR) journals, Cancer epidemiology, biomarkers & prevention. The article discusses the evidence surrounding overexpression of insulin-like growth factor (IGF)-I and how that is implicated in human pancreatic tumours. To look at this concept further, the researchers decided to use longitudinal data from a study involving 187 cases and 374 controls, a not insignificant number as a starting point:
"We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk."
Michael Pollak, one of the authors from McGill University in Montreal, is a recognised authority on the subject and gave a fascinating talk on the science and biology behind the topic at the AACR Lung cancer meeting back in January this year. It's a particularly interesting pathway, not only because of the potential for cross-talk between pathways, but also feedback and feedforward loops, especially with the insulin receptor (IR), as Pollak elegantly illustrated.
It was therefore with great curiousity that I downloaded and read the paper (see the clickable journal link in the reference below), wondering what they found in the broader study. Essentially, they concluded that:
"A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer."
Thus, rather than the absolute levels per se, the ratio may turn out to be a useful biomarker of the disease because the individual levels were not found to be helpful by the researchers, who:
"confirmed the nonsignificant associations for IGF-I, IGF-II, and IGFBP- 3 and risk of pancreatic cancer from previous studies."
As many of you know, pancreatic cancer is rather nasty, typically being diagnosed late because the symptoms can be subtle to detect and diffential diagnosis from other conditions associated with general malaise is hard. A new biomarker would be clearly be helpful, although the findings will need to be validated in future large scale longitudinal studies or from pooled analysis from other prospective trials.
Mind you, this research on pancreatic cancer reminded me of the phase I Merck study in the same tumour type, reported earlier this year, with a combination of different therapies including IGF-1R and EGFR inhibitors.
As far as I can remember, Merck also included the use of metformin in the protocol to manage hyperglycemia, which would also potentially block the IGF-1R – IR feedback loop seen in the figitumumab trial. Still, it would be interesting to know whether the IGF-I/IGFBP-3 molar ratio and free IGF were higher in the people with pancreatic cancer in that study.
Clearly, if IGF-I/IGFBP-3 turns out to be a valid biomarker of disease risk then it may be possible to identify, monitor and ultimately treat people with pancreatic cancer earlier, as well as develop better pipeline drugs, since we learn more about the biology of the disease in the process.
That can only be a great thing in the long run for improved outcomes.
Douglas JB, Silverman DT, Pollak MN, Tao Y, Soliman AS, & Stolzenberg-Solomon RZ (2010). Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 Molar Ratio and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology PMID: 20699371