Routine screening for most types of cancer does not exist today. With a few important exceptions, cancer screening has been a failure; even widely endorsed methods, such as breast and testicular self-exams and mammography, have come under fire. These tests miss too many cancers and pick up too many “false positives,” suspicious findings that turn out to be benign. The result: much anxiety, many unnecessary biopsies and exploratory operations-and relatively few cures.
The few existing blood tests for cancer aren’t any better. Take, for example, PSA, the test for prostate cancer, and CA-125, for ovarian cancer. Both are named after the proteins they look for, and both are terrible. PSA, which the American Urological Society recommends offering to every man over age 50, “misses about a third of patients with cancer,” says David Sidransky, a cancer researcher at Johns Hopkins, “and it falsely calls patients that are positive with PSA as having cancer about a third of the time.” For ovarian cancer, the picture looks even worse. Only about half of patients with early-stage ovarian cancer show elevated CA-125 levels, and the rate of false positives is high, because some benign conditions cause overproduction of the protein. As a result, CA-125 is only approved for monitoring the progression or recurrence of ovarian cancer, not for screening.
George Wright, a cell biologist at the Eastern Virginia Medical School in Norfolk, has spent his entire research career of more than 40 years trying to find better diagnostic markers for early cancer detection. He has been understandably frustrated. “Maybe a protein biomarker that [we] discovered would detect 20 to 30 percent, not 100 percent, of the cancers,” says Wright. Equally useless are markers that falsely diagnose healthy people as ill, regardless of how many cancers they reveal. To be useful for routine screening, a blood test for cancer has to be almost perfect.
In 1998, Wright read an article in a trade magazine about a biotech company in California that was looking at protein patterns; suddenly, that almost-perfect test seemed possible. The Fremont-based company, Ciphergen Biosystems, claimed that a few drops of blood could reveal hundreds of proteins simultaneously, when analyzed with a standard laboratory instrument called a mass spectrometer. The proteins, though, aren’t explicitly identified; instead, the machine prints out a pattern of sharp peaks and troughs, each peak representing the blood level of some unknown protein. Ciphergen thought that comparing the results from cancer patients to those from healthy subjects could aid the search for cancer biomarkers, because many proteins are overproduced in tumor cells. Properly identified and studied, those proteins could lead to better cancer tests. But Wright had an even bolder idea: the patterns themselves might provide a ready-made signature for cancer. The strategy of using patterns, if it worked, would shave years, even decades, off the time required to create a test, since it would eliminate the need to identify the individual proteins and perfect means to detect them.
Wright also suspected that tests based on cancer protein profiles could fingerprint cancer more accurately than any one protein. They “would be more effective than anything that was available,” he recalls telling Ciphergen’s CEO, who was skeptical. But Wright bought a Ciphergen machine in January 1999 and began looking for incriminating patterns himself.