Michael Jeltsch
    Ph.D., Adjunct Professor, Academy Research Fellow

    Translational Cancer Biology Research Program
    Institute of Biomedicine
    Biomedicum Helsinki

    P.O. Box 63 (Haartmaninkatu 8)
    FI-00014 University of Helsinki

    Tel. +358 2 941 25514
    Fax +358 2 941 25510



Alma-intranet Flammaintra

Drug Target Identification, Selection and Validation

Despite the bewildering amount of drugs that have been invented, there are still many diseases that lack any pharmacological treatment approach. And for many more the available options are suboptimal. Hence our interest in identifying, selecting and validating drug targets.That's the first step in drug development and together with the toxicology and pharmacokinetics data forms the preclinical phase of drug development. At the moment we focus on antiangiogenic cancer drugs, i.e. drugs that do not target the tumor cells directly, but that work by cutting off the blood supply to the tumor ("starving the cancer to death"). Why antiangiogenic cancer drugs? Even though there are effective antiangiogenic cancer drugs on the market (e.g. Avastin™), they are not as good as they potantially could be.

VEGFs and VEGF Receptors as Drug Targets

Jeltsch GroupFigure 1. The VEGFs and angiopoeitins and their receptors are the major anti-angiogenic drug targets.

Cancers are dependent on Vascular endothelial growth factors (VEGFs): VEGFs make the blood vessels grow, that support the cancer with nutrients and oxygen and allow it to grow. There is already a drug targeting VEGF-A (Avastin™), which helps cancer patients to stay alive longer.

Jeltsch GroupFigure 2. Initially anti-VEGF-A cancer drugs are effective, but tumors can develop "resistance" by expressing VEGF-C.

However, most cancers become sooner or later resistant to Avastin™. There is good evidence that cancers become resistant by using VEGF-C instead of VEGF-A. And there is no cancer drug on the market that universally targets VEGF-C. So far, nobody has been succesful in generating a drug effective against all forms of VEGF-C ("pan-inhibitory antibody"). We want to develop a biotherapeutical drug to fill this gap. Such drug would would - similar to Avastin™ - broaden our toolkit to fight cancer and increase the survival rates for many patients.