A promising new cancer drug will soon enter Phase 2 clinical trials after success in animal modelling and preliminary human studies,media New Atlas reported. The drug, known as AMG 510, targets a genetic mutation that is one of the most common causes of cancer.
Mutations in genes called KRAS cause up to 20% of human cancers, especially leukemia, colorectal cancer, lung cancer and pancreatic cancer. Unfortunately, until now, effective treatment has not been widely available.
The problem is that the KRAS protein structure is too smooth. Typically, proteins have “small pockets” on their surfaces, while drug molecules are designed to lock proteins to function. But there doesn’t seem to be a “base” for drugs on KRAS. A team from the biotech company Amgen used X-ray crystallography technology from Berkeley Lab Advanced Light Source (ALS) to examine a specific KRAS mutant protein called KRAS (G12C). The technology created a high-resolution map of the structure of the protein – and, to be sure, they found “small pockets” that had previously been missed.
Later studies enabled the team to study molecular interactions and design drugs that would be appropriate for this situation. The end result of several years of work is the AMG 510, which binds to the “pocket” and locks the protein in an inactive state.
Researchers found A KRAS (G12C) mutation in about 13 percent of lung adenocarcinomas, 3 percent of colorectal cancers and 2 percent of other cancers, meaning AMG 510 is a promising potential treatment.
In earlier studies, the drug was shown to reside on KRAS (G12C) and bind effectively to it, causing tumors in mice to shrink. With these results, the U.S. Food and Drug Administration (FDA) quickly tracked AMG 510 as a treatment for metastatic non-small cell lung cancer with a KRAS (G12C) mutation that previously could not be treated by other methods. It has now been approved for Phase 2 clinical trials. This makes AMG 510 the first treatment for this common cancer cause and enters clinical trials.
The results of the earlier study were published months ago in the journal Nature.