Home > Dr. Ward's Newspaper Column Home > 2010
Genetic profiling to diagnose and treat cancers
May 03, 2010Once in a while the origin of a cancer eludes us. The primary tumor, the starting place, may be overgrown by metastatic cancer, thus hiding it from identification. Or, maybe, the primary tumor is growing much smaller than the metastases and isn't identifiable yet. On a rarer occasion, the immune system may have caught up with the primary cancer, eradicating it, but the metastatic sites proved beyond the immunity's capabilities.
The dilemma that this poses is that without knowing what kind of cancer we are dealing with, we often don't know how to most effectively treat it. Pathology has tools to identify tissue-specific proteins on cells that may suggest where it came from. But there are times we give up, call it a "carcinoma of unknown primary and treat it with a toxic kitchen sink of chemotherapy called the Vanderbilt Regimen. Sometimes the Vanderbilt Regimen is a home run. Most times it isn't, and when it fails to work, there are no other drugs approved for a cancer orphaned by its primary. That's about to change.
A new diagnostic test has been developed to identify a primary in these cancers. It is novel in its approach to this small group of cancers, but it's the future that it portends that piques my greater interest in it. The test is named CancerTYPE ID. It is a molecular classification tool that measures and catalogues the activity of 92 genes. It compares the profile of a cancer of unknown primary against a data set of thousands of known cancers in order to ferret out the likelihood that it is any of 54 different cancers. That is pretty cool, and on the “once in a while" occasion that we are puzzled, it's a valuable tool. But it's what's around the corner from CancerTYPE ID that excites me.
Just as diagnostics is moving towards identifying abnormal gene expression and mutation, so is therapeutics. An increasing number of the arrows in our quill of cancer drugs are designed to target the abnormal activity of a particular mutated gene. As we collect more of these tools, the temptation to completely revolutionize cancer classification to accommodate the optimal use of these drugs will become necessary. We already sub-classify tumors in this way. Twenty percent of breast cancers abnormally over-express the gene Her 2neu, and we treat it with Herceptin and Tykerb, drugs that target the Her 2neu protein. Most colon cancers have a mutation in a gene called KRAS. Those that don't are more likely to respond to the drugs Erbitux and Vectibix.
A future with molecular therapeutics would work like this. Once discovered, a cancer would be biopsied and a genetic profile would be run, identifying all of the essential mutations that made a normal cell become cancer. Some of the mutations would have led to accelerated growth. Others rendered the cancer invasive, allowing it to spread and scatter or to grow its own blood supply, necessary to metastasize. In some cases we may biopsy a tumor again when it recurs to see what new mutations it has developed in the interim. Of course lung cancers will tend to have certain mutations profiles and stomach cancer's another, but ultimately an individual cancers genetic makeup will be its defining feature.
Once catalogued, a treatment regimen specific to the combination of mutations found in that particular cancer would be devised, taking care to avoid overlapping toxicities as much as possible. We would anticipate that, in contrast to today's chemotherapies, a treatment targeted to the cancer's specific genetic footprint may have very limited side effects.
In this scenario the life of cancer patients and their doctors will change dramatically. It allows us to envision treatments that though they may not always cure, will be tolerated for years, decades, and lifetimes of suppressing the cancer, changing it from a terminal illness into a chronic disease and requiring us to reexamine the term malignancy.
As patients focus on a full lifespan, doctors will turn from a job where an inordinate amount of time is spent reacting to the cancer and side effects of treatment, to one of engineering and executing personalized treatment plans. The Vanderbilt Regimen will become a historical footnote, and kitchen sinks will be relegated to being just a plumbing fixture.
Dr. Ward is a medical oncologist at Puget Sound Cancer Centers. He can be reached at (425) 775-1677.