Or how to tell a cell protein that he should stop calling. We're just not that into you. There have been a lot of acronyms and medical terms floating around lately and it's been a bit of a jumble, but it's finally starting to make some sense. First, let me show you the picture Dr. Bendell drew for us.
The big circle is a cell and the circled N at the bottom is the nucleus. Remember that for growth to happen, cells have to divide or produce something else. What makes cancer a problem is that those cells grow faster than normal and they don't know when to quit. In Rich's case, the cell is question is a tumor cell from his appendix that is desperately trying to produce slime. There aren't a lot of those cells, but they are creating a big messy byproduct all over the place.
Ok, back to the picture. All that alphabet soup inside the cell is a collection of proteins. They create pathways to the nucleus with information telling it what to do, generally if it should grow or produce something (e.g. slime). Let's focus on the list on the left. It says:
RAS RAF MEK ERK
In real life, the road is a little more winding, but you can pretend it's a straight line like that. Dr. Bendell called it a telephone game, where RAS tells RAF tells MEK tells ERK that tells the nucleus to grow. Rich's RAS is mutated (hence the M pointing at it) and stuck in the on position so it just keeps telling the proteins below it to keep producing. If he had done the monoclonal anti-body treatment they discussed in Maryland, it would have done no good because it targets stuff right outside the cell (that Y looking thing). RAS would has kept on spamming down the line and the cells would have kept producing.
The drug trial we are going to start this week inhibits the ERK protein, so that it will hopefully ignore the repeated messages of the mutated RAS protein and ideally the nucleus would chill out and stop producing mucin. The cells that we're targeting are the appendix cells that got scattered all over Rich's abdomen and are mutated and constantly deciding to make more mucus. If we can tell those cells to chill out, then the mucus won't grow. There is also a hope that without growth, the mucus could slowly be reabsorbed back into his body.
Those letters on the right are another pathway to the nucleus. It is possible that if we block the ERK, the cell could get all huffy and find a new way to tell the P13K to tell the MTOR to tell the AKT to tell the nucleus to grow. The other study Dr. Bendell was investigating was one that targeted both the MEK and the P13K proteins (so both pathways), but that trial isn't available until July and she didn't want to wait that long. They did not expect to have an opening in the ERK trial but one happened on Thursday so they eagerly jumped on it.
As Dr. Bendell said, if we can get to the point where there is no growth with this drug, she's happy. If we find that there is actual shrinkage then she's extra super happy. But we have to just play it by ear. If the drug makes Rich feel awful or he's just tired of flying to Nashville, we'll reassess. But for now, this is the best plan.
We talked a bit about the strong language in the trial. She laughed and said they all sound like that but she feels like this is very safe. She said the drug companies will be all spastic when a drug is first being administered and she will tell them, "Yes the patient received the drug. Miraculously, the patient's head is still attached!" Everything is super new technology, but we feel safe.
Tuesday is the day of a thousand pre-trial tests. Rich has an eye exam, MRI, x-rays, and a CT scan. There is a slight chance we could start the drug trial on Wednesday but they need a room to be available. Right now it looks like Wednesday will be our day to work from Tennessee and then start the trial on Thursday.
I'll update more on our accommodations and other interesting details of this trip, but as Ian would say, I'm tuckered after all that. And we thought we would never use biology in the real world.