How a BTK inhibitor works

In the average healthy adult between 50 and 70 billion cells die each day due to apoptosis (cell death). B-cells, which are lymphocytes, are part of the immune system. When a person gets a cold, these white blood cells increase, attack the germs, and when they have done their job, they die. All it takes is a mistake in one cell that leads to the cloning of white blood cells that do not die. It is just bad luck.

There has been a decade of scientific research supporting the importance of the B-cell receptor signaling pathway in rapidly out-of-control growing B-cells (leukemia). Dr. Michael Keating from Houston’s M.D. Anderson was the first physician to tell Carl and I about the new drug PCI-32765, which was later named “Ibrutinib.” I remember the excitement in his voice when he showed us photos of before and after lymph nodes, and exclaimed, “This is what you need!”

The proteins in my leukemic white blood cells prevent cell death, so they continue to proliferate in my blood, my lymph nodes, and my organs. Because, quite frankly, blood runs through every organ of your body. The white blood cells crowd out healthy red blood cells and platelets and enlarge lymph nodes, which often affect blood circulation. With a weakened immune system, there is constant worry about getting infections.

BTK is an essential kinase (a type of enzyme) in the signaling pathway downstream of the B-cell receptor. The pathway in which BTK is involved turns several protein enzymes that prevent cell death either on or off.

Scientists are hoping that Ibrutinib, which is a BTK inhibitor, will target the pathway and not affect other organs or tissues of the body. When Ibrutinib molecules target and irreversibly bind to the kinase, it will do so for as long as 24 hours, which means I have to take the drug every day until it stops working.

When Ibrutinib is ingested in the body, the leukemic white blood cells in the lymph nodes dump into the blood stream. This causes a temporary increase in white blood count (WBC) for about two months. When the drug blocks BTK, it induces cell death in white blood cells that refuse to die and the cells leave the body.

That, my friend, is how it is theoretically supposed to work.

Since I am experiencing the mutation in which the short arm of chromosome 17, where the gene for p53 resides, is deleted, my B-cells are free of the tumor suppressor. This is not good, and is a poor prognosis. This is what some of my doctors have termed “a true death sentence.”

However, I beg to differ… I do not believe I have been given a death sentence. I believe Ibrutinib has just given me a life sentence.