Most of us probably learned about the scientific method in grade school: ask a question, do research, construct a hypothesis, test it to see if it works, analyze results, and communicate the conclusion. We also probably learned that even when your experiment doesn’t turn out the way you expected, the results are still important!
This is also true in academic medicine. When researchers work to develop an effective new treatment, they often start by testing out specific chemical compounds and their effects on cancer cells. Researchers have to rule out hundreds or even thousands of compounds before they find one that works. This is a very long process, and from the outside, it can sometimes seem like nothing is getting done. However, the process of elimination is crucial to discovering new treatments! Every compound crossed off the list gets researchers one step closer to their ultimate goal: finding effective, safe treatments for childhood cancer.
One example is the discovery of All-Trans-Retinoic-Acid (ATRA), which is used to treat Acute Promyelocytic Leukemia (APL), which is a unique subtype of Acute Myeloid Leukemia (AML). In the 1970’s, children diagnosed with APL were considered very high-risk cases. Only about 50% made it to complete remission, and many relapsed or suffered significant side effects. Researchers who were studying the cellular structure of APL discovered that APL had a high number of “immature” cells, meaning they replicated very quickly. They realized that certain compounds might be able to make these cells “differentiate,” or mature, so they behaved more like normal cells. After testing hundreds of compounds like butryrate, hypoxanthine, and dimethyl sulfoxide, they landed on ATRA. ATRA was a vitamin-A derivative that caused APL cells to “differentiate,” dramatically reducing the spread of the cancer. ATRA has far fewer side effects than conventional chemotherapy, and it was nearly miraculous in treating the disease. Adding ATRA to standard treatment increased the remission rate from about 50% to almost 90%.
In order to find ATRA, researchers first had to eliminate hundreds of other compounds that failed to work with APL. Researchers could have considered these other compounds “failures,” but we prefer to think of them as necessary steps along the way toward the development of a new treatment. At CureSearch, we know that the road to a life-saving discovery is paved with these failures.
Breitman, T. R., Stuart E. Selonick, and Steven J. Collins. “Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid.” Proceedings of the National Academy of Sciences 77.5 (1980): 2936-2940.
Breitman, T. R., Steven J. Collins, and B. R. Keene. “Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid.” Blood 57.6 (1981): 1000-1004.