Researcher outlines drug potential in targeting receptor
how IGF-1 receptor and the IRS-1 protein act as a key growth factor
that regulates cell and body size. The discovery has revealed
details as to how tumour cells proliferate and spread.
The discovery is important as it adds another piece of the cancer puzzle. It was discovered that when IRS-1 was activated with the IGF-1 receptor, ß-catenin, a protein important in colon and breast cancer is turned on.
Previous studies by Baserga's team discovered that normal cells lacking the IGF-1 receptor gene could not be made to turn cancerous. It was found that when IGF-1 receptors in cancer cells were knocked out, the cells self-destructed.
This meant the IGF-1 receptor was somehow necessary for tumour cell growth. This discovery could be of use to pharmaceutical companies who are interested in targeting the IGF-1 receptor with the idea of killing cancer cells.
Baserga told DrugResearcher.com: "A drug could work just by inhibiting the receptor, thus forbidding the receptor sends no signal."
"A number of companies have tried to contact me regarding the use of my reagents (cells and plasmids). These include Amgen, Merck, Novartis, Novo Nordisk, and AstraZeneca," he added
Baserga added that although pharmaceutical companies were interested in targeting the IGF-1 receptor he had no plans to commercialise his research.
Baserga, who pioneered much of the understanding of the basic behaviour of the IGF-1 receptor, used knockouts - specially bred mice lacking a particular gene - to develop a cell line without IGF-1 receptors.
Normal cells grew, but would not turn cancerous when placed in rodent cells with added cancer-causing genes.
The finding suggested that if cells that lacked IGF-1 receptor could not be turned cancerous, perhaps cancerous cells with IGF-1 could be reversed.
"If this is true in humans, then this is a rational target, he commented. "Studies by companies in the last few years have found that antibodies and various small molecules made to the IGF-1 receptor kill cancer cells without toxicity, he added.
"The general idea is that if you find something that knocks out the IGF-1 receptor, you will kill the cancer cells and have only a modest effect on normal cells - at least using cells in culture and in mice," he said.
Several years ago, for example, Baserga and his group used antisense therapy to target the IGF-1 receptor, which killed cancer cells in mice but didn't work as well in people.
However, clinical trials are just beginning, he says, and he is still hopeful that other approaches will work in humans.
