How Our Understanding of Chronic Myelogenous Leukemia Developed Precision Medicine
Prevention & Treatment There's a lot of enthusiasm for precision oncology. Here is an overview of how it works and how those results impact real people.
Precision oncology is a general term indicating that, with newer techniques and ongoing discoveries in modern biology, we can know more precisely the behavior of any one patient’s cancer, and then design treatment around this level of information. Thus, the treatment is “precise” for an individual’s cancer, and precise regarding our treatments for that group of cancers.
We call the group of cancers “hematologic malignancies,” or “blood cancers.” Those include Hodgkin’s disease, Non-Hodgkin’s lymphoma, multiple myeloma and acute and chronic leukemias. In solid tumors (like lung, melanoma) we have had a lot of success in targeting specific proteins to treat these cancers.
Precision oncology came of modern age with the discovery of the Philadelphia chromosome in a blood cancer, called chronic myelogenous leukemia or CML for short.
Figuring out CML
One of the leukemias that had a slower pattern of growth this cancer has had a long and interesting history, dating back to the 1800s — when it was characterized after the microscope was invented and used to look at the blood for the first time. Over time, more information was learned about this cancer.
At first, we had no great treatment for CML, although rare patients were cured with a bone marrow transplant in the 1970s. Then we used medicines like daily interferon shots — the same substance your body makes when you have a flu which caused similar symptoms in our patients — to control the disease.
“What we are achieving with the new era of precision oncology are, for one thing, better treatments that can sometimes cure a patient.”
The modern era of precision medicine in cancer came about with the discovery and, over time, of the protein bcr-abl and its role in causing CML cells to grow. Scientists noted a chromosome rearrangement called the Philadelphia chromosome. Later this was identified as a specific protein in the cancer cells, called bcr-abl. In the 1990s Dr. Brian Druker led the clinical trials that used a medicine, imatinib, that was ultimately proven to control (and probably cure) patients with CML with just a pill.
The case of APL
A rare leukemia called acute promyelocytic leukemia (or APL) has undergone dramatic changes with precision oncology. This used to be a cancer where patients died within a month of diagnosis. However, with more modern treatments, including the discovery of a precise target in acute promyelocytic leukemia, we now can cure these patients 80 to 90 percent of the time. With a molecular target identified, a drug called ATRA (all trans retinoic acid) was subsequently introduced in 1985 to specifically attack the cancer cells of patients with APL.
Application to cancer in general
By refining our treatments over time, we have dramatically changed the landscape for this blood cancer to include those higher cure rates and fewer side effects. Because cancer is a collection of cells with different changes in their DNA (mutations), precision medicine gives us more information about what these changes are and how to treat them. Testing of a patient’s cancer with molecular testing helps doctors to pick the right treatments.
In the past decade, we have seen several new drugs approved for a blood cancer called multiple myeloma, and numerous breakthrough drugs in Non-Hodgkin’s lymphoma and Hodgkin’s disease.
What we are achieving with the new era of precision oncology are, for one thing, better treatments that can sometimes cure a patient. We are also realizing treatments with fewer side effects, like well-tolerated pills. A third element is the faster discovery of better treatments for patients.
These are truly exciting times for patients with hematologic cancers, and all those who care for them. Seeing real progress is exciting for all.