Cancer pre-treatment improves drug delivery
enhance the delivery of drugs to tumours, improving the treatment
of solid cancers while also reducing side effects.
The novel approach, developed at University of Illinois and Chicago Labs, takes advantage of a unique property of tumour blood supply which means that drugs can be preferentially delivered to blood vessels supplying the cancer tissue.
The discovery hinges on the discovery of two different receptors of endothelins, one of the most potent substances affecting blood vessels. The endothelin A receptors are located on smooth muscle cells and are responsible for blood vessel constriction, while endothelin B receptors are found on the endothelial cells lining blood vessls and cause them to relax.
Spectrum has licensed rights to a series of endothelin B agonists, which cause blood vessels to dilate. Because solid tumour blood vessels grow rapidly they lack smooth muscle and nerve systems that would also control the constriction or relaxation of vessels, so these agents act preferentially at these sites, increasing blood flow - and the delivery of the cancer drug - into the tumour.
In animal models of human cancer, administration of endothelin B agonists prior to treatment with the widely used cancer drug paclitaxel increased the levels of paclitaxel in the tumour by more than 400 per cent, while not significantly affecting paclitaxel concentration in normal tissues. In addition, the effectiveness of paclitaxel in reducing tumour volume was more than doubled using this approach.
Dr Luigi Lenaz of Spectrum explained that one of the significant limitations of chemotherapeutic agents is their poor selectivity, so doses that are required to kill tumour cells cause unacceptable toxicities to normal tissues.
"Endothelin B agonists have been shown to selectively enhance delivery of chemotherapeutic agents to the tumor tissue … which in turn results in marked increase of therapeutic effect, while drug concentrations in normal tissues are not significantly affected," he said. He added that the approach could prove to be broadly applicable to many chemotherapeutic agents and tumour types.
Under the terms of the agreement, Spectrum acquired an exclusive worldwide license to endothelin B agonists for the treatment of cancer, including treatment of solid tumours. Chicago Labs will receive an upfront fee of $100,000, as well as payments upon achievement of certain development, regulatory and sales milestones, plus royalties.
