New Treatment Targets Most Aggressive Forms of Leukemia

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Active substance overcomes treatment resistance in Philadelphia chromosome-positive leukemia.

Active substance overcomes treatment resistance in Philadelphia chromosome-positive leukemia.

Researchers have developed a new active substance that effectively fights the most aggressive forms of Philadelphia chromosome-positive leukemia (Ph+).

While the cure rate of patients with Philadelphia chromosome-positive leukemia has sharply grown over the past several years, a high percentage of patients have developed medication resistance for some current treatments. As a result, the combined efforts of haematologists in Germany working with a Russian pharmaceutical company sought to develop a treatment for the resistance, both in vitro and in vivo.

The Philadelphia chromosome causes patients to develop chronic myelogenous leukemia or acute lymphatic leukemia, which are the first types of the disease that are treatable with molecular therapy that targets the cancer-inducing gene BCR/ABL.

Over time, however, the treatment becomes ineffective due to BCR/ABL mutations or other as of yet unknown mechanisms. Ponatinib, the only drug currently able to overcome nearly all clinical resistance, unfortunately carries some life-threatening side-effects.

Subsequently, researchers developed an innovative kinase inhibitor, PF-114, that seeks to match the effect of Ponatinib on Ph+ leukemia, but with reduced side-effects. Interntional phase 1 studies are expected to being in the first half of 2015.

"These results provide the basis for the administration of PF-114 in treatment-resistant patients with Ph+ leukemia,” said researcher Martin Ruthardt, MD, in a press release. “The favorable efficacy and good side effect profile now need to be further tested on patients in clinical phase I studies.”

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