Science Breakthroughs Revisited: A Cancer Killer Cancer researcher Ira Pastan tried combining a toxin that kills cells with a type of antibody that targets certain cells. The idea was to create a "cocktail" that would seek out cancer cells -- and only cancer cells -- and kill them with the toxin. It's been 10 years since Pastan first tried this method. Did it work? Well, yes and no...

Science Breakthroughs Revisited: A Cancer Killer

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We hear about exciting science news all the time, except often the news is about something that might happen. A new gene discovery might lead to a cure, or a new way of breeding mosquitoes might eliminate malaria.

Well, NPR's Joe Palca looks back on a number of scientific stories like this that he reported on a decade or more ago to see how often the might happens materialized.

JOE PALCA: In 1996, I reported on a promising new approach to treating some of the most deadly cancers, including breast, ovarian and colon cancer. Ira Pastan and his colleagues at the National Cancer Institute hoped to use cancer patients' own immune systems to fight their tumors. Scientists knew that when people get cancer, they produce antibodies that try to attack the tumors.

But the antibodies alone just aren't strong enough to kill the tumors. Pastan hoped they could give these antibodies some extra punch by attaching a toxin to them. Here's Pastan in 1996.

Mr. IRA PASTAN (National Cancer Institute): This toxin is a very powerful cell killing agent, and if you inject a small amount into mice, it kills mice by killing all the cells in the liver because it homes or targets to the liver. So we use genetic engineering to redesign it, so instead of going to the liver, it goes where our antibodies sends it, for example to cancer cells.

PALCA: The first antibody-toxin combination was called LMB1. It only worked in a few patients. Still, other cancer researchers were impressed with Pastan's early results. Here's Arthur Frankel, a cancer researcher at the Medical University of South Carolina in 1996.

Mr. ARTHUR FRANKEL (Medical University of South Carolina): Well, I think he has really made in many respects a quantum leap of advancement in the field. I think he's at least 50 percent of the way towards, you know, a final construction that should be helpful to a number of patients.

PALCA: Ten years later, Pastan is still at the National Cancer Institute, and he's still working on an approach to cancer treatment that involves arming immune cells with a toxin. Things didn't quite work out for LMB1 the way he hoped in 1996.

Mr. PASTAN: We published a paper, I think in Nature Medicine, showing it had some activity, but there were problems with it.

PALCA: So Pastan and his team made several new versions of LMB1. LMB2 through LMB6 never made it out of the lab. LMB7 made it to patients, but it had problems. This is a familiar pattern for medical scientists - try something in the clinic, find problems, back to the lab, make some changes, then back to the clinic. Ultimately, they reached LMB9 and there the process stalled.

Mr. PASTAN: We did clinical trials with LMB9. And before seeing any anti-cancer activity, we saw renal toxicity and stopped the trial.

PALCA: Renal toxicity means kidney problems. In other words, Pastan and his team were successful in arming human antibodies with special weapons, but before the armies got to the tumors, they attacked another mass - the kidneys.

But Pastan hasn't given up on the concept of attacking tumors by linking a toxin to an antibody. He and his colleagues continue to modify the antibody toxin molecule, hoping to find a version that will only target tumors. The latest iteration is called SS1P.

Mr. PASTAN: We've now finished two clinical trials with SS1P. We reported some of this data at meetings, but we haven't written up full papers yet. But I can say there's enough activity, anti-tumor activity in humans, to justify going on to phase two trials.

PALCA: Phase two trials means that SS1P would be tested in more people. So Pastan's a little bit further along in 2006 than he was in 1996. Pastan's experience with his new approach to treating cancer is a reminder why breakthrough is a word most scientists are loathe to use. Progress is rarely made in a single, giant step.

Joe Palca, NPR News.

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