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Inhibiting PI3 kinase by involving the tumour microenvironment is an innovative concept for treating chronic lymphocytic leukaemia (CLL)

(Vienna, 15.10.2010) Inhibiting PI3 kinase by involving the tumour microenvironment is an innovative concept for treating chronic lymphocytic leukaemia (CLL)Dr. Medhat Shehata of the Department of Medicine I, Division of Haematology/Haemostaseology at MedUni Vienna demonstrates in the latest edition of the renowned medical journal "Blood" how targeted apoptosis (programmed cell death) can be induced in cancer cells in chronic lymphocytic leukaemia (CLL) without damaging the surrounding healthy tissue. It will soon be possible to use this targeted, gentle form of therapy in everyday clinical practice.

As shown by the latest findings, the environmental milieu (microenvironment) plays a substantial role in the development, proliferation and metastasation of different neoplasias. Here tumour cells not only use mitogenic messenger substances such as cytokines and hormones but also anti-apoptotic signals to obtain an advantage of survival. The precise mechanisms at the molecular level are largely unknown, but Dr. Shehata and his team have been able to make a major discovery in this connection.

In a standardised co-culture system (tumour and milieu) which is based on the situation in the body it has been shown that the signal exchange between leukaemia cells and the environment mainly takes place via the PI3 kinase signal transduction pathway. With targeted pharmacological/genetic inhibition of PI3 kinase, programmed cell death is induced in CLL cells without affecting the surrounding healthy tissue cells. In addition, this work reveals that reactivation of the tumour suppressor gene PTEN, by pharmacologically inhibiting the PTEN regulating kinase CK2, acts synergistically in combination with PI3 kinase inhibitors. These findings could provide the first basis for a tailored therapy for the world’s most common form of leukaemia. In addition, this concept could also be extended to many other tumour entities and thus forms the basis for innovative medication development programmes.

One specific benefit of this co-culture system is that clinically relevant results can be achieved outside the field of animal testing. On the basis of this promising data it is realistic to assume that forms of therapy can be developed in the near future which can be implemented clinically. This would allow a breakthrough in the therapy of chronic lymphocytic leukaemia and possibly other forms of cancer. Dr. Shehata's work was recently published as the cover story in the internationally renowned medical journal "Blood".

Shehata M, Schnabl S, Demirtas D, Hilgarth M, Hubmann R, Ponath E, Badrnya S, Lehner C, Hoelbl A, Duechler M, Gaiger A, Zielinski C, Schwarzmeier JD, Jaeger U. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the anti-apoptotic effect of human stromal cells in chronic lymphocytic leukemia.
Blood. 2010 Oct 7;116(14):2513-21.