On the first day of the month, my husband will often repeat the words rabbit rabbit; as he did on Friday. There is an old superstition that doing so on the first of the month is good luck. It also happened to be April Fools’ Day and a snow day (no school). Nature’s little joke.
On Thursday Alice (Dr. Shaw) called me with some news. Several months ago I had a needle biopsy to try to determine why I was developing resistance to crizotinib. Alice thought it likely that there would be evidence of a further mutation. However, the report came back negative. She recently ordered another test on the sample and on this go around it was positive for a mutation (which could have been missed the first time due to dilution of the tumor sample by the presence of normal cells or inflammation).
So I am a mutant mutant. The ALK mutation remains and continues to be responsive to the crizotinb, however the new mutation is characterized by unresponsiveness. As of now, it is a unique mutation (for the moment, it’s all mine) and though the researchers have pinpointed the location, it doesn’t yet have a moniker.
So what does this mean?
Basically, although initially stopped in its tracks, the cancer found a way around crizotinib. Imagine water dammed by a mortared stone wall. Should a crack develop, water will first leak and then eventually rush through the hole. Crizotinib was, for a time, a perfect patch. However, the cancer, much like water would, continued to apply pressure to the resistance; in effect, searching for the path of least resistance. Eventually a secondary mutation developed, the wall was breached, and the cancer no longer completely contained.
It would be tempting to imagine cancer as somehow sentient in the face of such terrifying persistence. In reality, the fact that cancer operates on a cellular level confers what seems to be an unfair advantage.
Luckily, my very sentient oncologist is also quite persistent. Click here for a link to a recently published paper on EMLK-4 ALK that Dr. Shaw co-authored. Oh–the image of the lungs contained within the paper belongs to yours truly (c’est moi).
So is it a good thing or a bad thing to be a mutant mutant? I suppose one con is that my cancer might be characterized as more aggressive, given that it has already mutated. On the other hand, the original mutation responded dramatically to crizotinib. Had no further mutation been found, the next line of treatment likely would have been Alimta (a non-targeted therapy) in conjunction with crizotinib. Now there is a distinct possibility that an HSP-90 or new generation ALK inhibitor will be added to my existing regimen. There will once again be a specific target (or, rather, two targets).