Energy boost: the Warburg effect returns in a new theory of cancer.

proposed that cancer was caused by altered metabolism— deranged energy processing—in the cell. Warburg, winner of a Nobel Prize in 1931, is now considered by many to be the greatest biochemist of the first half of the 20th century. His cancer theory, though, mostly fell on deaf ears. Altered metabolism " may be a symptom of [cancer], but not the primary cause, " wrote fellow biochemist and Nobelist echoing the majority viewpoint. Warburg went to his grave in 1970 insisting he was right, but for 30 years his cancer theory appeared to be buried along with its originator. Now Warburg's theory is enjoying a resurrection. Two prominent cancer biologists contend that a shift in energy production from oxidative phosphoryla-tion to glycolysis—the so-called " Warburg effect " —is a fundamental property of cancer cells, not just a byproduct of the cell's transformation into cancer. " We think it's a requirement of transformation, " said University of Pennsylvania cancer biologist Craig Thompson, M.D. " You can't become fully transformed until you've had this shift. " If Thompson is right, the implication is enormous: a whole new area of vulnerability for cancer cells, one that promises novel targeted treatments. " Can we exploit any of this for therapeutic reasons? " asked in Baltimore who is doing similar work. " The answer is going to be yes. " But there is hardly consensus on that viewpoint. Cancer biologist Robert Weinberg, Ph.D., of the Whitehead Institute at the Massachusetts Institute of Technology in Cambridge, is one prominent skeptic. " To date, the weight of evidence indicates that the shift to 'aerobic glycolysis' is an epiphenom-enon of cell transformation rather than a causally important process, " he wrote in an e-mail. Weinberg, though, concedes that Thompson " may have some new evidence [for] a causal role. " Power Supply More than 60 years have passed since biochemists detailed the two main ways to generate energy, in the form of adenosine triphosphate (ATP), in normal cells: oxidative phosphorylation in mitochon-dria and glycolysis in the cytoplasm. All cells use both pathways but rely overwhelmingly on oxidative phosphorylation, switching to glycolysis at times of oxygen deprivation. (Marathon runners and other endurance athletes benefit from this shift.) Warburg showed that many tumors relied on glycolysis even in the presence of oxygen—the Warburg effect. " He made the fundamental observation that holds up today, " said Thompson. But the true reasons …