Why do some cancers come back? Sometimes, a treatment can effectively eliminate cancer cells to undetectable levels, but, if the treatment stops, cancer may return. This is the case with chronic myeloid leukemia treated with drugs known as tyrosine kinase inhibitors. These drugs have dramatically improved clinical outcomes and generated unprecedented rates of complete responses and long-term survival. To achieve these results, patients have to take the drug for the rest of their lives. "Clinical trials testing the effect of discontinuing the drug have shown that at least half of the patients achieve treatment-free remission, but in the other half the cancer returns," said Daniel Lacorazza (photo), PhD, Associate Professor of Pathology & Immunology at Baylor College of Medicine and Principal Investigator in the Experimental Immunology & Hematology Laboratory at Texas Children's Hospital. "We think that relapse occurs because tyrosine kinase inhibitors affect most chronic myeloid leukemia cells, but not leukemia stem cells. It's like removing the tree, but leaving the roots that can sprout new shoots." Leukemia stem cells are an elusive, small cell population that initiates and sustains leukemia. Stem cells can regenerate via a poorly understood mechanism of self-renewal and enter a path of development that gives rise to new leukemia cells. Dr. Lacorazza and his colleagues think that clues to treatment-free remission might be found in this little known, self-renewal mechanism. "The results of the drug discontinuation trials suggest that a cure may not be possible with tyrosine kinase inhibitors alone.
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