If we as a country invested our entire ground-transportation budget inimproving automobiles, leaving no money for maintaining highwaysand bridges, we might after 25 years end up with amazingly efficientcars, but no way to drive them from here to there.

This simple scenario appears embedded in an editorial, in today'sScience, under the title: "Delivering molecular medicine to solidtumors."

Its author, tumor pathophysiologist Rakesh Jain, of Harvard MedicalSchool, compares this imaginary automotive gridlock to oncology'scurrent inability to deliver cancer-killing agents into solid tumors.

"The present generation of molecular biologists, cell biologists,geneticists, immunologists and oncologists," Jain wrote, "is quitefamiliar with the molecular aspects of neoplastic diseases, but has amuch more limited knowledge of the integrative pathophysiology ofsolid tumors."

He observed that 85 percent of the cancers that cause one-fourth ofall deaths in the U.S. are solid tumors, half of whose patients will dieof their disease.

"Leaders in government, academia and industry," Jain's editorialasserted, "must confront the following reality: After we havesystematically dissected a tumor to determine which genes aremutated, and can successfully predict the lifetime chances of anindividual's getting a tumor on the basis of their genetic profile, thepatient is told that we have a set of wonderful molecular agents butcannot deliver them to all target cells in the solid tumors in effectivequantities."

One likely reason, he pointed out, is that "many tumors resistpenetration by anticancer agents, which may help explain why drugsthat eradicate malignant cells in vitro often fail in the body."

Jain told BioWorld Today that, "For 30 years, our knowledge ofcancer has gone up exponentially at the molecular biology level,beyond any expectations, beyond any dreams, frankly."

Those promises, he added, "were made by the researchers to thepublic, the policy makers and the investors. And the chances are,from what these guys are offering, they're not going to cure cancer inthe near future."

Jain would probably say that his apparent pessimism is really that ofan optimist in possession of the facts.

He addressed his down-beat remarks last November to a meeting inBaltimore on "Cancer: Interface Between Basic Science and Clinic,"sponsored by the American Association for Cancer Research.

"I put it to half a dozen extremely well known people there," Jainrecalled: `Your work is so elegant, but how is it going to make anydifference to treatment?' They were all offended. They told me,`Well, it may have an effect on prevention.'"

To that observation, the Harvard researcher replied: "Look, thebiggest prevention target sitting in front of us is called cigarettesmoking. We haven't done nearly enough with that, so how are yougoing to prevent solid tumors?"

Cancer biologist Bert Vogelstein, a Howard Hughes Medical Instituteinvestigator at Johns Hopkins University, organized that meeting."He really got me going," Jain said. "Bert encouraged me to write upmy views, and offer them to Science."

Vogelstein told BioWorld Today, "I certainly have reviewed [hispaper] and thought it made valid and important points." The Hopkinsinvestigator is widely reputed to be a founding father of the p53tumor suppressor gene.

Commenting on the points Jain made, he said: "It's generally felt, atleast among investigators in the field, that there has been a realrevolution in cancer research over the last decade or so. One couldsummarize that revolution in a single sentence: Cancer is in essence agenetic disease."

Vogelstein added, "What appears to be the primary force drivingmolecular events is mutations in growth-controlling genes, not justtumor-suppressor genes, but oncogenes as well. That clearly, at leastin my mind, lies at the heart of cancer.

"But that doesn't mean," he concluded, "that cures for cancer areright around the corner. It's a whole different business to understanda disease, and then try to do something about it. That requires asmuch imagination, hard work, luck and all the rest as finding thebasis for the disease."

Jain's recipe for breaking out of the basic-science/clinical-curedichotomy, "in today's climate of shrinking federal research support"is creating "a consortium of pharmaceutical and biotechnologycompanies producing agents for the detection and treatment ofcancer, along with the federal government and private foundations."

Such an alliance, he suggested, would undertake formal trainingprograms "where scientists and clinicians are educated about thebiochemical and physiological barriers to successful cancertreatments. That way, the large investments in cancer biology willeventually be rewarded, and future anticancer agents will live up totheir tantalizing potential." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.