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Successful Cancer Therapy May Doom Later Treatments To Failure

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Shimmying through shrinking blood vessel pores is just one of many challenges facing drug agents. Ten years ago, Jain showed that just getting into the blood supply surrounding the tumors is a difficult task. "Nobody had measured resistance to blood flow in tumor vessels before. It was like walking into a wide open field," he says. Jain and his colleagues showed that the capillaries, arteries, and veins surrounding tumors are a jumbled mass -- thick in some areas and pinched at others -- rather than a neat and orderly array. And to make navigation even more difficult, the blood flowing through them is highly viscous -- more like sludge than water.

Blood vessels surrounding tumors are also known to be very leaky in some areas but not in others. It was only recently with the development of his immune-deficient mouse model that Jain was able to grow enough kinds of tumors to tackle the question of blood vessel pores systematically. He and his colleagues injected fluorescently labeled particles of increasing size in to the blood vessels of the six tumors at various locations and watched to see which ones got out. They used the same approach to see the effects of tumor shrinkage.

Even if drugs are designed that can get through pores, they will face an uphill battle once they get inside a tumor. The pressure exerted by the material surrounding tumor cells, called the interstitium, is enormous, as Jain and his colleagues have recently shown. Jain believes that there are ways around such obstacles. For example, it may be possible to lower pressure by draining the interstitium inside tumors. In fact, Jain and his colleagues are currently working on such a tumor drain. "We are trying to understand and modify the barriers more and more," he says.

The research was funded in part by the National Cancer Institute and the National Institutes of Health.

Editors: A two-color graphic that helps illustrate this research is availab
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Contact: Bill Schaller
schaller@hms.harvard.edu
617-432-0441
Harvard Medical School
14-Apr-1998


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