Drug companies look to biomarkers to salvage cancer target

Abstract

The announcement last month that the biotech powerhouse Amgen was terminating a late-stage pancreatic cancer trial added another blow for drug developers hoping to halt tumor growth by blocking the protein known as insulin-like growth factor 1 receptor (IGF1R). In 2010, Pfizer abandoned its IGF1R-targeting antibody called figitumumab after phase 3 trials failed to demonstrate signs of clinical efficacy. And in the two years since, several other drugmakers have discontinued their own earlier-stage programs directed at the same target. With the phase 3 failure of Amgen’s ganitumab, “the field of IGF inhibition is at a crossroads,” says Milind Javle, an oncologist at the MD Anderson Cancer Center in Houston who is running a clinical trial involving the Merck IGF1R blocker dalotuzumab. “This should serve as an example for us that we will not achieve success [with IGF1R inhibitors] unless we identify patients with predictive biomarkers who will benefit. There’s really no alternative. We have to do it.” A promising potential biomarker that could help parse out patients who would benefit most emerged in July when a team led by Raju Kucherlapati, a cancer geneticist at the Harvard Medical School in Boston, published the largest genome-wide analysis of colon and rectal cancer to date. The group’s analysis of 276 samples revealed that insulin-like growth factor 2 (IGF2)—a hormone that binds IGF1R to promote cell division—was overproduced in tumor samples from 22% of study participants (Nature 487, 330–337, 2012). “We think that all of those 22% of the patients could benefit from the inhibition of either IGF2 or its receptor,” Kucherlapati says. However, the biomarker approach is far from a sure bet. In a study reported earlier this year at the American Society for Clinical Oncology meeting in Chicago, researchers found that people with colorectal cancers with high amounts of IGF2 responded badly to Merck’s dalotuzumab. By comparison, people with the same tumor type showing elevated levels of a related protein, called IGF1, typically fared better on dalotuzumab than those without the predictive biomarker. Given the mixed results to date, scientists say that more biomarker discovery trials are needed. Paul Haluska, an oncologist

DOI: 10.1038/nm0912-1312a

Cite this paper

@article{Dolgin2012DrugCL, title={Drug companies look to biomarkers to salvage cancer target}, author={Elie Dolgin}, journal={Nature Medicine}, year={2012}, volume={18}, pages={1312-1313} }