This blog is the final post of our four-part "Gene" Fridays series on cancer genetics.
The dream Dr. Bert Vogelstein and his team hope to realize is prevention. He doesn’t expect to prevent cancers from occurring, but by using cancer genome sequencing, he believes there is an opportunity to prevent cancer deaths. He envisions safe, simple, and inexpensive tests that would allow doctors to find, diagnose, and eradicate cancers in their very earliest stages.
Cancer, he says, takes decades to spread, transforming into the lethal stage known as metastasis where it invades other tissue and organs. “It takes about 30 years for a cancer to go from its submicroscopic stage to a full blown metastatic cancer capable of killing a patient,” says Dr. Vogelstein. “The last stage of metastasis, where the cancer spreads, the stage that actually kills people, occurs in the last few years of this 30-year process.”
Take colon cancer, for example. According to Dr. Vogelstein, of the 55,000 people who die each year, nearly all of the deaths occur because the cancers were not detected until this final stage. If the cancers were detected before cancer cells spread outside of the place they began, most patients could be cured with surgery and drug treatment or potentially even surgery alone.
This is easier said than done, Dr. Vogelstein admits, but he and his team have focused their efforts on developing such cancer screening tests. The tests they are researching are different than the cancer screening tests currently being used. Cancer screening tests in use today, such as PSA for prostate cancer and fecal occult blood for colon cancer, are undeniably useful, but they are not specific—many non-cancer conditions can cause a positive result. The tests the Vogelstein team is developing are definitive indicators of cancer, as they detect the genetic alterations that actually cause the cancer. The challenge is determining the blood and body fluids from which this cancer DNA could be easily extracted and ensuring the test is sensitive enough so it does not miss genetic alterations.
Scientists in Dr. Vogelstein’s laboratory have modeled one of their new tests off of the Pap test, the widely used test to screen for cervical cancer. Dr. Isaac Kinde, a young scientist in the Vogelstein-Kinzler laboratory, envisioned using molecular genetic technology to develop a similar test for ovarian and endometrial cancers. Testing the same cervical fluids gathered in Pap tests, the new test, which Dr. Kinde calls the PapGene test, detected 100 percent of endometrial cancers and over 40 percent of ovarian cancers in pilot studies. They continue to refine the test to improve its sensitivity to detect the earliest changes in the cancer process. Dr. Vogelstein envisions such tests becoming a regular part of annual physical exams. “People normally give blood, stool, urine when they visit their doctors. Women have Pap smears, and smokers may provide sputum samples. All of these could be examined for mutations,” says Dr. Vogelstein. He is hopeful that the ongoing work in his laboratory will result in gene-based cancer screening tests that will make possible the detection of cancers in an early and highly treatable stage.
If he is right, the coming decades will see dramatic decreases in cancer deaths. Some of the change will come through improved gene and immune-targeted therapies, but the biggest differences will be made, Dr. Vogelstein predicts, through early detection and prevention. “The history of medicine shows that when a disease is understood, it eventually becomes manageable,” says Dr. Vogelstein. “In public health, what has most reduced deaths is preventative techniques, not cures We still can’t cure polio. We can’t cure a massive heart attack or stroke, but we can prevent them, and that has led to their decreased incidence. I think the same will happen with cancer.”