Looking and listening
By Robert Levy
Biomarker research helps scientists tune in to tumor growth
Cancer has a reputation for stealth, a silent submarine of a disease that lurks and grows undetected before revealing itself. But the truth is that, in a biochemical sense, many cancers aren't quiet at all.
Their presence can trigger an alarmed response from the body, which may dispatch tumor-fighting agents and endeavor to choke off the malignancy's blood supply. Cancer cells themselves teem with proteins and other compounds that offer hints of the cells' intentions, hardiness, and vulnerabilities.
For years, doctors and scientists have sought to identify these telltale compounds – technically known as biomarkers – to get an early "read" on whether a tumor is present, how quickly it is likely to grow and spread, and how it will respond to therapy. They've identified dozens, the best known of which may be the prostate specific antigen, or PSA, a substance whose blood level can indicate the presence of prostate cancer.
Today, biomarker tests are used for several forms of cancer. However, most are far from 100 percent reliable, which is a serious shortcoming. Even a 90 percent accuracy rate would mean 100,000 of 1 million people tested would receive false results – and would then need further exams to prove or disprove cancer's presence.
"The term 'biomarker' applies to a range of substances – DNA, RNA, proteins, or other compounds – that can be measured as indicators of health or disease," says Dana-Farber's Charles Fuchs, MD, MPH, who leads research in the field. "In a disease as complex as cancer, there is a role for them at virtually every stage of treatment."
The term 'biomarker' applies to a range of substances – DNA, RNA, proteins, or other compounds – that can be measured as indicators of health or disease.
Though they come in many forms, biomarkers have three main uses in cancer medicine and research: determining whether an individual is at risk for or has developed a malignancy, predicting the course of disease, and deciding on proper treatment. Patients may be most familiar with the first application – diagnosing new cancers and recurrences. But the latter two uses, known as prognostic and predictive, respectively, are becoming increasingly important as cancer medicine moves into the era of personalized therapy, where treatment is tailored to the genetic makeup of each patient's tumor.
Biomarkers are hardly reclusive; they may be found in the bloodstream and, of course, in tumors themselves. They also can reside in the normal, healthy organs of people with an inherited predisposition for developing certain types of cancer.
An ideal blood biomarker would enable physicians to detect cancers when they're small and relatively easy to treat. Even the minutest tumors release proteins and other compounds into the blood that betray cancer's presence. The challenge is to detect these changes amid the normal ebb and flow of substances in the bloodstream. Because some of the changes are very subtle and vary from tumor to tumor, determining which are truly indicative of cancer is daunting. Imagine a modest uptick in the number of blue bicycles on the streets of Manhattan. Then think of the difficulty not only of discovering this increase but of determining what it means – rising gasoline prices, a fitness boom, a growing concern with the environment? Researchers encounter the same type of ambiguities in biomarkers, but with far higher stakes: markers are useful only if they point to cancer, particularly to tumors that are aggressive or malignant.
The search for biomarkers in tumor tissue faces similar hurdles. Technology has made it possible to take the genetic fingerprints of cells, the unique pattern of active genes within them. Researchers hope to use this information to classify tumors not just by the organ where they originate or their appearance under a microscope – the traditional identification method – but by their individual genetic identity, and to devise specific therapies for them. The difficulty lies in the sheer volume of data. A typical study may turn up hundreds of molecular variations between one type of tumor and the next. Culling the meaningful differences – the true biomarkers – from the far more numerous normal ones is an ongoing quest.
Biomarker research at Dana-Farber Cancer Institute runs the gamut from molecular probes of tumor tissue to the development of blood tests for different types of cancer. In many cases, biomarkers are tools of scientific research, enabling investigators to identify new subtypes of cancer and gauge the promise of new therapies.
