New Substance Overcomes Treatment-Restistance In Leukemia

New Substance Overcomes Treatment-Restistance In Leukemia, Philadelphia chromosome
Philadelphia chromosome (Image source)
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 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.
The 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 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, the researchers noted.