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New substance overcomes treatment-resistance in leukemia

Date:
November 28, 2014
Source:
Goethe-Universität Frankfurt am Main
Summary:
Haematologists have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukemia.
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Haematologists from Goethe University Frankfurt, working with a Russian pharmaceutical company, have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukemia.

The chances of patients with Philadelphia chromosome-positive leukemia (Ph+) being cured has greatly increased in recent years. Nevertheless, a high percentage of patients have developed resistance to available medication. But now, haematologists from Goethe University Frankfurt, working with a Russian pharmaceutical company, have developed a new active substance that effectively combats the most aggressive forms of Philadelphia chromosome-positive leukemia, both in vitro and in vivo. They have reported this in the current edition of the specialist journal 'Leukemia'.

Patients with the Philadelphia chromosome develop chronic myelogenous leukemia (CML) or acute lymphatic leukemia (Ph+ ALL). These are the first types of leukemia that are able to be treated due to the development of targeted molecular therapy. Selective kinase inhibitor active substances act directly on the cancer-inducing gene BCR/ABL. However, after a while, the treatment becomes ineffective for many patients -- either due to BCR/ABL mutations or due to other mechanisms that are as yet unknown. At present, there is only one substance, Ponatinib, which is able to overcome nearly all clinical resistance. Unfortunately, Ponatinib can only be used with extreme caution due to some of its life-threatening side-effects.

Moscow-based company Fusion Pharma has developed an innovative kinase inhibitor, PF-114 with the aim of having the same effect on Ph+ leukemia as Ponatinib, but with reduced side-effects. In the current edition of 'Leukemia', the team led by Dr. Afsar Mian, Professor. Oliver Ottoman and lecturer Dr. Martin Ruthardt from the Haematology Department of Medical Clinic II, have reported that PF-114 is as effective as Ponatinib against resistant Ph+ leukemia.

"These results provide the basis for the administration of PF-114 in treatment-resistant patients with Ph+ leukemia. The favourable efficacy and good side effect profile now need to be further tested on patients in clinical phase I studies," explained Dr. Ruthardt. "PF-114 would not have reached this level of development without our colleagues in Frankfurt. On the basis of this data, in the first half of 2015, we will be able to start international phase I studies," explains Dr. Ghermes Chilov, CEO of Fusion Pharma, the company that financed the project.


Story Source:

Materials provided by Goethe-Universität Frankfurt am Main. Note: Content may be edited for style and length.


Journal Reference:

  1. A A Mian, A Rafiei, I Haberbosch, A Zeifman, I Titov, V Stroylov, A Metodieva, O Stroganov, F Novikov, B Brill, G Chilov, D Hoelzer, O G Ottmann, M Ruthardt. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome- positive (Ph ) leukemias harboring the T315I mutation. Leukemia, 2014; DOI: 10.1038/leu.2014.326

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Goethe-Universität Frankfurt am Main. "New substance overcomes treatment-resistance in leukemia." ScienceDaily. ScienceDaily, 28 November 2014. <www.sciencedaily.com/releases/2014/11/141128111330.htm>.
Goethe-Universität Frankfurt am Main. (2014, November 28). New substance overcomes treatment-resistance in leukemia. ScienceDaily. Retrieved April 25, 2017 from www.sciencedaily.com/releases/2014/11/141128111330.htm
Goethe-Universität Frankfurt am Main. "New substance overcomes treatment-resistance in leukemia." ScienceDaily. www.sciencedaily.com/releases/2014/11/141128111330.htm (accessed April 25, 2017).