Hot Paper: Antiangiogenic Drugs

By Dilys Chan

Dr. John Ebos, a postdoctoral fellow in the lab of Sunnybrook Research Institute senior scientist Dr. Robert Kerbel, is the lead author of an article that is the second-most-cited biology paper published in the past two years.

The journal Cancer Cell published the paper “Accelerated Metastasis After Short-Term Treatment With a Potent Inhibitor of Tumor Angiogenesis” on March 3, 2009. Other researchers have cited the paper 134 times* in the 19 months since its publication.

“The reason this study has gotten so much attention—along with its companion paper published by another lab, which ranked first in the same survey—is because it discusses a very controversial topic in the field of angiogenesis inhibition,” said Ebos.

Antiangiogenic drugs, which regulators approved relatively recently, block the blood vessel growth that is necessary for tumours to grow and survive.

“While such drugs can work very well in certain instances, they may have little effect or even negative effects in others, and thus may have limitations overall—particularly in the treatment of early-stage disease,” said Ebos.

“While our study was only conducted in mice, the attention it received was also due to several coinciding high-profile clinical trial failures using these types of drugs," said Ebos. "Those trials in turn stimulated discussion and debate within the field about why these drugs are not working in certain circumstances—such as in early-stage colon cancer—and, critically, how they could be made to work better for patients.”

With the high number of citations that the paper has received, Kerbel said that there is a take-home message behind it: “I would hope that my colleagues in the cancer research community will appreciate the importance of undertaking preclinical experiments in mice which more accurately duplicate the circumstances of treating cancer in patients.

“We actually tried to model adjuvant therapy in mice, where we treated microscopic early-stage metastatic disease, including right after surgically resecting primary tumors, as is done in the clinic. This has rarely been done in the past by other preclinical investigators,” he said.

He added, “This is the sort of work that should have been done by companies before initiating hugely expensive long-term randomized phase 3 trials of adjuvant therapy using antiangiogenic drugs.”

*Thomson Reuters, October 10, 2010