Sleen's K-Ras Mutation

What follows is a mash-up of what I learned from the book, "The Emperor of All Maladies," from discussions with my immunotherapy fellow at NIH, and from email correspondence with my new cyber-pal, known as DK37*.

K-Ras is considered an oncogene (a gene that can cause cancer).  Colon cancer patients' DNA is typically checked in the earliest days after diagnosis to determine whether the patient is "K-Ras wild-type", or "K-Ras mutated".  I was found to be K-Ras mutated back in September, 2013 after my initial surgery.  I didn't know much about it at the time, except for the fact that certain drugs that have been found to be effective for "wild-type", would do nothing for me.

As part of the clinical trial at NIH, exomic sequencing was done, which identified my tumors' specific mutations.  The researchers found over sixty mutations, but one stood out as particularly interesting to them.  It was a mutation in the K-Ras gene.  It is referenced this way:  codon 12 G12D, and I was told that it is one of the most-common mutations in colorectal cancer (CRC). This designator is explained (ha, sort of) as: On the 12th codon, the twelfth amino acid "G" (glycine) has been replaced by "D" (aspartic acid). "D replacing G"--that is the mutation. 

Glycine, I was told, is a small, uncharged amino acid. Aspartic acid, on the other hand, is large and carries a negative charge (the charge is due to a carboxylic acid side-chain, according to my friend the medicinal chemist). Anyway, the negative charge blocks a cell's normal "stop dividing" instruction. The cell's "off switch" is effectively ignored, and so growth continues unchecked, forming tumors that grow without ceasing.

Fortunately for me, the tumors in my lungs have grown very slowly.  I would like to think that this is because I have been producing large numbers of tumor infiltrating lymphocytes (TILs) all along, but I have no way of knowing.  The aim of the clinical trial is to find TILs that are already working to remove cancerous cells in the patient, to multiply those, and to return them to the patient.  "Building up the army", is how many people think of it.

The researchers had success in the lab!  They discovered TILs in the harvested lung tumors that recognize the mutation in the K-Ras gene and are "reactive" to it.  If the 148-billion TILs they returned to me on July 1 are as effective in me as they were in the lab, we should expect to see shrinkage of my lung tumors by 12-weeks post-cells.  This is my great hope!  Alas, there are no guarantees.

* Super Genius