Diagnosis, Targeted therapies: Targeting activators, Sawyer 3
Professor Charles Sawyer explains that the CML clone makes mistakes in DNA replication and generates a diverse repertoire of mutations.
Charles Sawyer, M.D. is professor of medicine and director of the Prostate Cancer Program Area at U.C.L.A. Johnsson Comprehensive Cancer Center, and an investigator of the Howard Hughes Medical Institute. He works on therapies that target specific mutations in prostate cancer and chronic myeloid leukemia (CML). Here he describes his work developing a targeted therapy for CML patients with resistance to the anti-cancer drug Gleevec. â€œThey come about most likely because in the process of growing, the CML clone makes mistakes in DNA replication and generates a diverse repertoire of mutations â€“ most of which are probably irrelevant and just disappear but under the face of selective pressure of a drug, you get outgrowths. They get a growth advantage and they grow up. What's I think is clear is the drug itself is not causing mutations; it's not mutagenic. And when we look using very sensitive tools, it looks like the mutations are already there in most patients and so the die might be cast early on in the disease and it speaks to the need of having perhaps a cocktail of drugs to combat this much like the treatments for HIV virus is based. Well, I can give a number but the natural history of CML is actually a little different now in 2004 than it was four years ago because essentially everyone is now on Gleevec. But if you start on Gleevec in the late stage of the disease, 100% of patients have a resistance within about a year or two. If you start Gleevec at the beginning of the disease, about 15% have resistance within three years. We don't know beyond that what will happen but the curve seems to be continually dropping down gradually but there's no evidence that anyone's been cured with Gleevec and when we use PCR to look for residual CML cells in patients, even those that are doing fantastic, we still see residual cells by PCR. So, most of us believe that there's a reservoir of CML cells left escaping Gleevec, not necessarily expanding but just sitting there. And whether or not that reservoir will be a big problem in another five years of follow-up, we'll just have to see.â€
chronic myeloid leukemia, cancer drug gleevec, prostate cancer program, howard hughes medical institute, cml patients, dna replication, comprehensive cancer center, hiv virus, sensitive tools, charles sawyer, gleevec, selective pressure, prostate cancer, mutations, leukemia
- ID: 1015
- Source: DNALC.IC
1014. Diagnosis, Targeted therapies: Targeting activators, Sawyer 2
Professor Charles Sawyer explains that Gleevec is a pill taken once a day and works remarkably well in all phases of CML.
1016. Diagnosis, Targeted therapies: Targeting activators, Sawyer 4
Professor Charles Sawyer explains that EGF receptor happens to be the driver in at least 10% of lung cancer patients in the U.S.
1013. Diagnosis, Targeted therapies: Targeting activators, Sawyer 1
Professor Charles Sawyer explains that CML stands for chronic myeloid leukemia, which is a blood cancer and it is different from many cancers because it starts very slowly and patients when they're first diagnosed don't have many symptoms.
1012. Diagnosis, Targeted therapies: Targeting activators
In this section learn that tyrosine kinases are a family of activator proteins that trigger the cell signaling process leading to cell growth and division.
1010. Diagnosis, Targeted therapies
Conventional cancer drugs are cellular poisons that block replication or some other aspect of cell growth. These drugs affect all cells – healthy or cancerous.
15057. Before and after Gleevec, Brian Druker
Brian Druker talks about the drug he developed as a turning point in the war on cancer.
15082. Shutting down cancer with Gleevec, Brian Druker
Brian Druker reflects on the importance of understanding the causes of cancer for developing new treatments.
15054. Restoring hope with Gleevec, Brian Druker
Brian Druker talks about how Gleevec has restored patients' hope for the future.
16109. Sense of urgency, Brian Druker
Brian Druker talks about sense of urgency.
15994. The chronic myeloid leukemia (CML) mutation
View the animation to learn about the Philadelphia chromosome, the abnormal chromosome that causes chronic myeloid leukemia.