An experimental drug created by Jude Canon and his colleagues from the biopharmaceutical company named Amgen is said to bind the G12C mutation and stop it from working selectively.
The G12C mutation is found in around 13% of lung adenocarcinomas, which is a type of non-small-cell lung cancer, 3% of colorectal cancers and 2% of other solid tumors.
How the drug can shrink tumors
This drug can help shrink tumors that are caused by genetic mutation responsible for a lot of different cancers, giving way to greater personalized treatment of the disease.
Jude Canon stated that one in four human cancers have a mutation in their KRAS gene, and it is responsible for a protein that controls cell growth. These mutations can cause normal cells to grow out of control and eventually lead to cancer. He also said that patients with KRAS mutant tumors have a poorer prognosis, and they have lacked effective treatments.
However, finding a way to target this protein has remained elusive since it was discovered over 30 years ago.
Canon and his colleagues made a breakthrough when they found a way on the surface of the KRAS protein with the G12C mutation. When the researchers tested the drug, called AMG 510, they found that 8 out of 10 mice became cancer-free with a high dose.
The researchers also studied the effects of AMG 510 on four people with non-small-cell lung carcinoma. After six weeks, one participant on a 180-milligram dose had their tumor shrink by 34%, and another participant taking a 360-milligram dose saw their tumor shrink by 67%.
The other two participants saw no change, as their tumor did not decrease nor increase, and they both took 180-milligram doses.
Canon and his colleagues also found that the AMG 510 appears to prime the immune system against cancer. After the drug has removed the tumors from the mice during their experiment, they tried to inject new tumor cells, but their bodies would not grow the tumor cells, which suggests that the immune system had adapted.
Simon Conn at Flinders University in Australia said that this experimental drug is remarkable. By pairing it with genetic profiling, this drug provides the best candidate for improving the personalized treatment of a range of common and rare cancers, particularly the non-small-cell lung carcinoma.
Improvement of health
The discovery of the AMG 510 drug and its preclinical evidence activity shows that it has the potential ability to induce tumor-cell killing as both a monotherapy and in combination with other therapies. Its impact on the immune system may render tumor cells, particularly those sensitive to immunotherapy. The early evidence of clinical activity of AMG 510 is also presented in the study.
The executive vice president of Research and Development at Amgen, David M. Reese, M.D., said that they are pleased to share how their team of scientists were the first to exploit the previously hidden groove on the protein surface to finally know a potential drug against the oncogenic protein. These scientific insights, together with the superb molecular engineering, paved the way for AMG 510 to be first to a clinic, where it has shown early evidence of clinical activity.
