But it is obviously not an easy task to develop Gleevec all at once. The research and development of Gleevec itself has gone through a long and tortuous road.
Since the discovery of leukemia, humans have been fighting against this incurable disease. In the 1950s and 1960s, the mainstream academic community generally believed that "viruses are the main cause of tumors." At this time, Nowell and Hungerford of the University of Pennsylvania Cancer Research Institute began to do something "heretical". They were trying to find changes in genetic material in tumor cells.
In 1973, Dr. Janet Rowley, a female doctor from the University of Chicago, also joined the research.
It was not until the 1980s, with the rise of oncogene research, that New Zealand scientist Dr. Annelies discovered that a homologous gene sequence C-ABL of human and mouse leukemia viruses was translocated from chromosome 9 to the long arm of chromosome 22. This conclusion indicated that the translocation of C-ABL led to the occurrence of CML.
It took a total of 22 years from the discovery of the Philadelphia chromosome by Dr. Nowell in 1960 to the confirmation by Dr. Janet Rowley in 1973 that the Philadelphia chromosome was caused by chromosomal translocation, to the discovery by Dr. Anneliese in 1982 that the oncogene C-ABL translocated and fused with BCR to cause continuous activation of tyrosine kinase, ultimately leading to the occurrence of CML.
The cause of leukemia was found, but it took nearly another twenty years to find a solution to this disease.
In 1993, at the age of 38, Brian Drucker came to Oregon Health & Science University in Portland to conduct scientific research on CML. During this period, Drucker and his colleagues in Boston developed a new method to measure the activity of the BCR-ABL enzyme using specially designed antibodies. This method is an invaluable tool for evaluating potential treatments for chronic myeloid leukemia. While finding this method, Drucker must also compete with competitors from other research centers to be the first to find such a drug that can inactivate the key enzyme to suppress cancer and allow the remaining healthy tissue to survive.
Nick Leyden, a biochemist at Swiss pharmaceutical company Ciba-Geigy, was an old acquaintance of Drucker. Nick called Drucker and told him that his company had what Drucker was looking for.
The drug is called STI571, which was the name of Gleevec during its development. Although it was accidentally synthesized by chemists at Ciba-Geigy while searching for a new anti-inflammatory drug, researchers found that STI571 inhibited the activity of the enzyme through in vitro experiments. However, they were not sure how to use this compound.
That is to say, at this critical moment, Ciba-Geigy possessed a key enzyme, and Drucker knew how to use this key enzyme. When the two met, it was like dry wood meeting raging fire, and a violent chemical reaction immediately occurred.
In August 1993, Drucker received the first batch of liquid STI571 samples and other candidate compounds from Switzerland. He used the enzyme detection technology he helped develop to confirm that STI571 could strongly inhibit the BCR-ABL enzyme.
But while the experiments were successful in the lab, the results on animals were less than satisfactory.
However, by 1997, Drucker had published a large number of related papers with collaborators from Portland and Switzerland. He believed that the compound STI571 was ready for human trials. But Novartis did not agree to conduct human trials at this time because in previous animal experiments, dogs that received intravenous administration always failed to solve the problem of blood clots at the end of the catheter, and when larger doses were injected into the dogs, the animals showed signs of liver damage.
If the situation could not be resolved, Novartis even suggested abandoning the project completely.
However, Novartis's retreat did not stop Drucker. After all, chemotherapy would also be destructive to canines. So he bypassed Novartis and directly applied to the U.S. Food and Drug Administration (FDA). In June 1998, after obtaining FDA approval, Drucker used STI571 to treat a 68-year-old Oregon man with chronic myeloid leukemia.
The effectiveness of the clinical treatment was naturally no problem, and the side effects that had occurred in previous experiments on dogs were no longer present. It can be said that this first clinical trial was a complete success.
As more and more leukemia patients voluntarily joined the clinical trials, the drug indeed achieved better efficacy. So in 2001, Novartis submitted the new drug application report to the FDA, and it was approved within two and a half months - this is the fastest drug review in the history of the FDA so far. It is also one of the few first-line clinical new drugs that have been directly approved in the form of a "green channel" after only passing Phase I clinical trials.
In May 2001, the U.S. government announced that the new drug—which Novartis marketed as Gleevec in North America and Glivec in Europe—would be used to treat patients with chronic myeloid leukemia.
This is the entire process of the development of Gleevec, which took nearly half a century and the total research funding exceeded 5 billion US dollars!
This drug is indeed the best drug for treating leukemia. Many leukemia patients in later generations can survive for five or six years after using this drug, even without bone marrow transplantation. Some patients can even survive for more than ten or twenty years.
Of course, the price of this medicine is also very expensive. At least in China, this medicine is definitely not affordable for ordinary people.
"Dying to Survive" was filmed based on the various incidents caused by this drug in China.
However, in this era, Gleevec has not yet been developed...
PS: I would like to thank "小鱼儿62" and "很懒的鱼" for their 100 rewards.
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