Beckwith H, Yee D. Were the IGF signaling inhibitors all bad? Molecular Endocrinology. http://press.endocrine.org/doi/abs/10.1210/me.2015-1157
Preclinical studies in the 1980s defined a role for insulin-like growth factor signaling in the development and sustainability of the malignant process.
Subsequently, antibody, tyrosine kinase, and ligand inhibitors of the insulin-like growth factor receptor were manufactured.
In the past decade, numerous clinical trials have tested the efficacy of insulin-like growth factor receptor inhibitors in the treatment of advanced tumors.
Early phase trials in heavily pretreated populations showed promise with complete or partial responses in a few patients and stable disease in many more. Unfortunately the results of the early phase trials did not pan out to later phase trials.
The lack of use of biomarkers to define subsets of patients that may benefit from insulin-like growth factor receptor blockade and compensatory signaling via other growth factor receptors such as the insulin, growth hormone, and epidermal growth factor receptors may have played a role in the lack of efficacy of insulin-like growth factor receptor inhibition in phase III trials.
Although these trials failed to show benefit, the trials have revealed previously unknown knowledge regarding the complex nature of insulin-like growth factor signaling. The knowledge obtained from these trials will be useful in designing future trials studying inhibitors of growth factor signaling.
Preclinical studies in the 1980s defined a role for insulin-like growth factor signaling in the development and sustainability of the malignant process.
Subsequently, antibody, tyrosine kinase, and ligand inhibitors of the insulin-like growth factor receptor were manufactured.
In the past decade, numerous clinical trials have tested the efficacy of insulin-like growth factor receptor inhibitors in the treatment of advanced tumors.
Early phase trials in heavily pretreated populations showed promise with complete or partial responses in a few patients and stable disease in many more. Unfortunately the results of the early phase trials did not pan out to later phase trials.
The lack of use of biomarkers to define subsets of patients that may benefit from insulin-like growth factor receptor blockade and compensatory signaling via other growth factor receptors such as the insulin, growth hormone, and epidermal growth factor receptors may have played a role in the lack of efficacy of insulin-like growth factor receptor inhibition in phase III trials.
Although these trials failed to show benefit, the trials have revealed previously unknown knowledge regarding the complex nature of insulin-like growth factor signaling. The knowledge obtained from these trials will be useful in designing future trials studying inhibitors of growth factor signaling.
