Drugs that successfully carve away at cancers of the lung, brain, breast, and other organs could be acting as double-edged swords, according to a new study by Massachusetts General Hospital and Harvard Medical School researchers.

The study, which appears in the April 14 Proceedings of the National Academy of Sciences, is the first to measure the size of the pores that line the blood vessels surrounding a variety of solid tumors. As solid tumors shrink, so do the microscopic pores in the blood vessels surrounding the tumors -- so much so that some tumor-killing agents may no longer be able to squeeze through vessel walls to reach their targets. In addition, first-time therapies may fail because therapeutic drug molecules are too bulky to pass through the blood vessel pores in the first place.

The findings suggest a fundamental change in the approach to designing chemotherapy agents. They may need to be smaller and more agile. "The public, investors, and the government are so enamored of the sophisticated new gene therapies. They're looking at Mercedes and Lamborghinis. But they don't think "can these new therapies get through the doorway?" says Rakesh Jain, the A. Werk Cook Professor of Radiation Oncology at Massachusetts General Hospital and Harvard Medical School.

Jain and his colleagues grew six different cancers in immune-deficient mice and measured pore sizes of surrounding blood vessels. The one human and five mouse cancers were grown at various places inside the mouse's body to represent what happens during metastasis. Working with hormone-dependent tumors, the researchers induced the tumors to shrink by cutting off their supply of hormones.

The researchers found that pore size varied among the six tumor types -- for example, mouse breast tumors had much bigger openings than mouse liver cancers -- and among sites within the same tumor. Solid tumors often contained a mixture of bigger and smaller openings. Pore size also varied depending o
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Contact: Bill Schaller
schaller@hms.harvard.edu
617-432-0441
Harvard Medical School
14-Apr-1998