kw: book reviews, nonfiction, medicine, cancer, genetics
In 2001 a new cancer drug, the first genetically-informed, targeted therapy agent, was approved in the US, Gleevec (or Glivec overseas). It was initially created to turn CML, Chronic Myeloid Leukemia, from a certain sentence of death into either a curable condition or one that a patient could live with. The substance has proven useful for several leukemia varieties and four or five other cancer syndromes. It works by deactivating a kinase (an energy transfer protein) that runs wild due to a specific genetic error. To date, it is the only targeted therapy substance that is anywhere near so effective. Patients who can tolerate the side effects (hey, if death is the alternative, I could tolerate a lot!) are not cured, but can live with the cancer for many, many years.
The chain of circumstance that led to Gleevec is exceptionally complex and convoluted, and the story is well told in The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level by Jessica Wapner. The Philadelphia chromosome was first seen in 1959. This refers to a shortened chromosome 22, and later it was found that the missing piece gets moved to the end of chromosome 9. The result is that two genes (or more accurately, protein coding regions) get jammed together and produce a very oversized kinase that ramps up cell energy use and turns it into a malignant cancer. Gleevec plugs the active site of the kinase, effectively silencing it. Cells that contain the mutation soon die.
I did not count, but many, many people were involved during the 42 years from the discovery of the abnormality until a clinical substance was produced and accepted for treatment by the FDA. I got this impression: something like 200 talented people putting together a 100,000 piece puzzle, where they first have to scour the countryside to find the pieces. And during final stages of the clinical trials, about a metric ton of the agent had to be produced to treat hundreds, then thousands, of patients for several months.
It is a good thing that Gleevec is useful for several conditions. The initial market for it was just a few thousand people. It was really hard for the researchers to get company buy-in to test the drug because it seemed they'd never recoup the research costs (say, a quarter billion dollars). As it is, staying alive with CML and its sister conditions costs more than $90,000 per year. This is the epitome of something Lewis Thomas once wrote about, that prevention is dirt cheap, most cures range from kinda cheap to affordable, but chronic care will break the bank.
Ms Wapner writes that the story has more characters than a Russian novel. That may be an understatement. I suspect Gleevec is the low-hanging fruit of genetic therapies, however. It involves a mutation you can see in a light microscope, and a protein that is comparatively easy to plug up. Cancer is proving a very tough, and costly!, nut to crack.