By Anthony J. Brown, MD
WESTPORT, CT (Reuters Health) – Some anti-angiogenic agents, used to disrupt the blood supply to tumors, appear to actually normalize it transiently. This could improve the delivery of chemotherapeutic drugs, suggesting a "new paradigm for combination therapy," according a commentary published in the September issue of Nature Medicine.
Dr. Rakesh K. Jain, from Massachusetts General Hospital in Boston, describes the paradoxical effect of anti-angiogenic agents and discusses the possible therapeutic implications.
"It is very counterintuitive that a drug which is supposed to kill blood vessels actually improves the vessels prior to destroying them," Dr. Jain told Reuters Health. "We first made this observation in 1998," he added. "I decided to write this commentary after several more experiments with different therapies revealed that this was a fundamental rather than an accidental finding," he said.
"While these agents do not completely reverse the abnormal vascular pattern found in tumors, they do normalize them," Dr. Jain stated. "This normalization facilitates chemotherapeutic delivery and it also allows oxygen to enter the tumor, which is necessary for effective radiotherapy," he said.
"The anti-angiogenic agents that produce this effect include a number of direct agents, such as anti-VEGF antibodies, and indirect agents such as Glivec," Dr. Jain pointed out.
"Further studies are needed to determine the timing of this anti-angiogenic-induced therapeutic window," Dr. Jain said. "We have characterized the window in animals, but we now need to study it in humans," he concluded.