In a path-breaking development, the deadliest protein in cells that triggers a third of all cancers, including lung, colon and pancreatic cancers, has been conquered by US researchers.
Their findings on the matter were presented in research papers published online Nov. 20 in the journal Nature.
The current buzz is around a protein in human cells called ras which in its mutated form can trigger the development of cancerous tumours, fuel their growth and keep them alive. All efforts to develop a drug to block this mutant protein have eluded the topmost scientists for more than three decades, leading many to believe it was unbeatable.
However, UC San Francisco researchers have finally found a way to deactivate the rogue protein, by making small molecules (chemicals) that destroy ras-driven human lung cancer cells. This UCSF research group is led by Dr. Kevan Shokat, a Howard Hughes Medical Institute investigator and chair of the UCSF Department of Cellular and Molecular Pharmacology.
Shokat has described the rogue gene as the “Everest of cancer mutations.” According to the American researcher, scientists have tried to drug every inch of the rogue protein ras. They have “looked at every nook and cranny on it and screened a million compounds and never found anything that inhibits it well [until now]…. We are very excited. We believe this has real implications for patients,” Shokat said.
Cancers caused by the mutant ras protein grow fast and spread faster and are difficult to treat. This includes lung, bowel and pancreatic cancers. Despite advances made in oncology, lung cancer is the leading cause of cancer deaths in the US, while colon and pancreatic cancers are the third and fourth leading causes of cancer deaths, respectively, in America.
In Britain alone, more than 150,000 die of these cancers in a year, which is one life every four minutes. Lung cancer is the leading cause of cancer deaths, killing almost 35,000 Brits a year. Bowel cancer is the second biggest cancer killer, with around 16,000 deaths annually.
It is hoped by inhibiting the mutant ras, the new drug will stop the growth of tumors and shrink them. Significantly, it targets only the cancer-causing form of the ras protein, while sparing the healthy, normal ones, thereby cutting the risk of side-effects.
Shokat, who co-founded a company called Araxes Pharma with a Johnson & Johnson subsidiary Janssen Biotech to commercialize his work, said: “What is very special about this drug is that it only works in cells that have this particular mutation. That distinguishes it from every other cancer drug we know of.”
Dr. Frank McCormick, an expert on cancer biochemistry, leading a $10 million-per-year US government initiative to tackle the ras gene, said: “Cancers driven by ras are the most difficult to treat. Dr Shokat and his team have taken a brilliantly innovative approach and have developed a strategy for targeting a mutant form of ras with exquisite specificity."
The latest drug works against one mutant form of ras, but Shokat believes it should be possible also to make drugs that work against the other forms. His molecules have so far been tested only on cells in a dish, but a new drug could be tested on humans in three years and on the market by 2021. However, it will have to be proven to be safe and effective in large-scale trials on patients.
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