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Cancer therapy -- Nanokey opens tumors to attack
Date:11/14/2012

There are plenty of effective anticancer agents around. The problem is that, very often, they cannot gain access to all the cells in solid tumors. A new gene delivery vehicle may provide a way of making tracks to the heart of the target.

Many types of tumor form a compact mass, like the phalanx formation of Greek antiquity. And although many drugs are known to be toxic to cancer cells, they are often unable to percolate into the inner recesses of the tumor. Upon intravenous administration, for instance, cytotoxic drugs may only be able to penetrate the outermost layers of a solid tumor. A team led by LMU pharmacologist Dr Manfred Ogris has now developed a new type of gene delivery vehicle, which is designed to open up a route through the vascular network that supplies the tumor so that drugs can reach their target.

Large tumors need a local blood supply for continued growth, and are capable of inducing the formation of new vessels. The resulting vasculature is more permeable than normal vessels, which should facilitate the delivery of cytotoxins. However, the lymphatic system does not work optimally in tumors, and back-pressure associated with the build-up of lymph limits the diffusion of drugs. As it happens, the cytokine Tumor Necrosis Factor α (TNFα), which can kill tumor cells directly, is able to increase blood vessel permeability as part of its pro-inflammatory function.

Shielding the organism from the drug

TNFα is already being used in combination with chemotherapeutic agents for the treatment of muscle tumors in arms and legs, but in this case, the local vasculature must be cut off surgically. "Unfortunately, therapeutically effective amounts of TNFα cannot be administered systemically, because this would lead to activation of, and damage to, all the vessels in the organism," says Ogris. "For this reason, it is not possible to use this approach on tumors in internal organs or against dispersed
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Contact: Kathrin Bilgeri
kathrin.bilgeri@lmu.de
49-892-189-6938
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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