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On the road to a new cancer therapy - starving the tumor

02.11.2007
Cancer is the major cause of death among men. Based on the current trends, scientists predict that, by about 2010, cancer will be the No. 1 cause of death for women as well.

VIB scientists connected to the Katholieke Universiteit Leuven, in collaboration with the Flemish biotech company ThromboGenics, have been studying the anti-cancer action of anti-PLGF.

This substance appears not only to be successful in the treatment of tumors for which the current therapies fail, but it also contributes to the greater effectiveness of existing chemotherapy, and still without side effects. Thus, anti-PLGF might possibly form the basis for a new treatment for cancer. This new finding, which is extremely important, was published in one of the most prestigious journals: CELL.

What is cancer?

Our body is built of billions of cells. Old or damaged cells are continuously being replaced, and cell division is strictly controlled, with new cells produced only as they are needed. However, this is not the case with cancer cells: cancer cells know how to circumvent the control system and go on multiplying out of control. The proliferating cells spread to surrounding tissue or are carried to other tissues and organs via the blood or the lymph system. This seriously disrupts our body’s vital functions - often with deadly consequences.

Blood vessel formation (or angiogenesis)

Every developing tissue is supplied with oxygen and nutrients via our blood vessels. But tumors grow much more quickly than normal tissues and so they have a greater need of nutrients. This is why, at a certain moment, tumor cells produce growth factors. These growth factors stimulate the formation of blood vessels that feed the tumor cells. In this way, even the innermost part of the tumor is supplied with nutrients.

Curbing blood vessel formation as a treatment for cancer

Peter Carmeliet and his colleagues are using this knowledge concerning the formation of blood vessels, or angiogenesis, to develop new therapies for cancer. Indeed, when the formation of blood vessels that feed tumor cells is blocked, the tumor starves due to the lack of oxygen and nutrients. The existing anti-angiogenesis drugs eliminate the most important angiogenetic growth factor. Unfortunately, this treatment induces side effects, and in addition the cancer compensates by producing other growth factors, so that the drug loses it effect. Therefore, new anti-angiogenesis treatments are needed urgently.

For several years now, the VIB researchers have been investigating a new angiogenetic growth factor: the placental growth factor, or PLGF. Oddly enough, PLGF only stimulates blood vessel formation in cancer and other diseases, but not in a fetus, young children or pregnant women.

New cancer therapy?

VIB researcher Christian Fischer and his colleagues - under the direction of Peter Carmeliet and in close collaboration with the biotech company ThromboGenics directed by Désiré Collen - have been studying the therapeutic possibilities of anti-PLGF, which retards the action of PLGF. Anti-PLGF not only increases the effectiveness of chemotherapy and the current anti-angiogenesis therapy, but it also inhibits the growth and metastasis of tumors that are resistant to existing drugs. In contrast to the current therapies, anti-PLGF does not trigger a ‘rescue operation’ in which other growth factors are produced as compensation. Another very important consideration is that anti-PLGF induces absolutely no side effects.

The favorable evaluation of anti-PLGF as a potential cancer treatment raises hope for a more effective cancer therapy with fewer side effects - which can be used with children and pregnant women, too. Furthermore, new results indicate that anti-PLGF can also be useful for the treatment of diseases of the eye that lead to blindness. ThromboGenics is focusing on the further development of anti-PLGF as a therapy. The company wants to begin the first clinical tests by the end of this year.

3D animation

Via www.youtube.com/watch?v=_ZEysIhDsok you can find a 3D animation which clearly shows the described research. Ask a high resolution version before November 1st via evy.vierstraete@vib.be.

Funding
This research has been funded by: the EC, ThromboGenics NV and BioInvent, Bristol-Myers-Squibb, German Research Foundation, AACR, EMBO, FWO, Leducq Foundation, Belgian Science Policy, DKH, GOA, IWT and FP-6-Angiostop, and VIB.

This research has been conducted by Christian Fischer and colleagues in Peter Carmeliet’s ‘Functional genomics of cardiovascular and neurovascular biology and disease’ research group in the VIB Department of Transgene Technology and Gene Therapy, K.U.Leuven – under the direction of Désiré Collen, who is also the CEO of ThromboGenics.

(For more info, see:
www.vib.be/Research/EN/Research+Departments/Department+of+Transgene+
Technology+and+Gene+Therapy/Peter+Carmeliet)

Evy Vierstraete | alfa
Further information:
http://www.vib.be
http://www.youtube.com/watch?v=_ZEysIhDsok

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