Cancer Biomarkers

Broadly defined, cancer biomarkers are biological markers that indicate the presence of a cancer, much like the tip of an iceberg. If these markers can be identified early enough, a disaster of titanic proportions can be averted. Cancer biomarkers can also offer additional clues about specific properties of the tumour, helping in treatment decision-making.

Cancer biomarkers are used to diagnose cancer, such as a tumor mass that is visible on an x-ray. But more recently, new biomarkers have allowed for even earlier detection of cancer. Progress is being made in different imaging techniques that allow better detection of tumors: 3D mammography results in 40% more detection of cancer and a reduction of 15% in callbacks for “suspicious” mammograms. Blood tests for high levels of prostate specific antigen (PSA) can indicate prostate cancer without ever looking at the prostate itself.

More recently, biomarker tests have been developed to test for a variety of genetic mutations that can make it very likely to develop cancer. The human genome was fully mapped in 2003, and now that we know what the different genes do, the next step is understanding what mutations in these genes can do. One high-profile example is the expression of the breast cancer, early onset (BRCA) gene, which has led some women (most famously Angelina Jolie) to have their breast or ovaries removed, rather than run the risk of potentially developing cancer.

The detection of cancer using early biomarkers has been controversial. Biomarker detection may lead to unnecessary treatment in patients who would have remained asymptomatic for the rest of their lives. On the flip side, these tests can provide a false sense of security in patients who unknowingly have cancer but do not have high levels of biomarker expression. In fact, some organizations are now cautioning against PSA screening.

We are increasingly discovering that tumor formation relies on a variety of factors, with no two cancers being alike. Knowing this, detection of specific biomarkers is immensely promising for developing treatments tailored to the specific properties of the tumor, leading to more effective treatment.

Take for instance the protein HER2 that is present on the surface of cells, and is responsible for cell proliferation.This protein is often overexpressed in breast cancer, and leads to increased cell division-- a hallmark of cancer. Because it is expressed at the surface of cells, it is easily accessible, and drugs such as Herceptin have been developed to inactivate HER2 in cancer patients. Testing patients for this disregulation in HER2 leads to effective personalized therapies.

Other biomarkers can indicate whether specific drugs will be ineffective. Similarly to Herceptin, Cetuximab is used to block the EGF receptor, which acts on KRAS and BRAF. However, certain tumors (30-50%) bypass the EGF receptor and have mutations in KRAS directly, rendering Cetuximab completely ineffective! Patients are now tested for KRAS mutations, and drugs have been developed that target KRAS directly.

Further developments in this field will allow us to identify more specific biomarkers, detect cancer earlier with higher fidelity, increase the personalization of medicine, and offer patients better treatment.

Many thanks to Clint Stalnecker, who presented a seminar on cancer biomarkers for the Cancer Resource Center.