A few weeks ago in the Guardian, I encountered an article with the intriguing title The epic battle with cancer’s Death Star. I correctly assumed the article would talk about KRAS, the protein that’s mutated in my cancer. The subtitle suggested that “Forty years after the mutant genes that cause the deadliest cancers were discovered, drugs that target them could be approved”. I dropped everything and basically ate my phone.
The story is well written, starting with the lucky postdoc who identified RAS as an oncogene, a protein that, when mutated, causes or at least accelerates some serious cancers. KRAS, a variant, is mutated in 56% of all colorectal cancers. In forty years of effort, the pharmaceutical industry has failed to develop a single drug that is specific for any of the RAS mutants. The protein is apparently too smooth, without surface features for small molecules to dock onto.
This picture has now changed slightly. Research has made progress. Molecules have been identified that bind to one particular KRAS mutant where the amino acid glycine at position 12 has been replaced by a cysteine. Amgen and Mirati Therapeutics have promising data from clinical trials. They plan to apply for approval for their drugs. Reading this far, my excitement had long cooled. I have a glycine at position 13 replaced with an aspartate. The drugs will have no relevance for me. The situation is as bleak as it was before.
There goes the second option. The third, which I’ve slowly been getting anxious about, is based on the molecular analysis of the liver biopsy. The idea is to extract tumor tissue (from my liver) and sequence the DNA for common cancer mutations. Cancer cells have impaired DNA repair processes and thus accumulate mutations as they proliferate. Most are detrimental. Cells with these mutations die off. Some help the cancer grow faster or fight the immune system or invade other tissues or attract blood vessels. Cells with these mutations will survive better, and the mutations, already known to medicine as cancer-promoting mutations, can be detected by DNA sequencing.
I had tumor tissue taken from my liver in the middle of February. Since then, I’ve been waiting for the results. At first, it took a while. Then my doctor went on a three-week vacation. When I saw him a day after his vacation, I understand that he hadn’t had the time to catch up on everything. But he promised to check up on the results and let me know.
He called me on Friday afternoon. “There are a few new mutations”, he said, “but nothing that would immediately suggest a therapy.” He said he would send the results to a colleague of his at the university hospital who is more experienced with this kind of analysis but wasn’t too optimistic. He also promised to give me the results for some digging. Maybe there’s a clinical trial somewhere that just happens to recruit patients right now. It wouldn’t be the first time.
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