If you were to ask your Primary Care Provider (PCP) this question, your answer would include information on your symptoms, lab test results, lifestyle, environmental exposures, and possibly the molecular biomarkers for your specific cancer. However, should you ask your Oncologist this same question, much of the information you’ll receive will concern molecular biomarkers.

Since you located this site based on your interest in cancer, we will focus on biomarkers in this section. The arrow below illustrates the many different areas that may be affected by using biomarkers in personalized medicine.

Image from the Personalized Medicine Coalition

We will briefly discuss all of these areas below and will cover them each in more detail as you move through this section of our website.

Early Detection Testing

As shown in the diagram above, early detection testing includes Risk Assessment, Prevention, and Targeted Monitoring. Although early detection testing will continue to be based on the risk averaged from a large population sample, the hope is that new tools will enable screening tests such as mammograms and colonoscopies to be more accurate and find disease earlier when it is easier to treat.

Risk Assessment

New forms of risk assessment will determine which people carry a genetic variation that may increase their risk for developing cancer. Enhanced means of 16 risk assessment will improve the ability to make informed life choices that may decrease a person’s risk. When individuals are found to have known variations, they should be monitored more closely based on evidence-based guidelines.

Although our genes influence our risk for cancer, much of the difference in cancer risk is due to factors that are not inherited. Although there is little you can do if you do have a specific genetic mutation, there are still steps that you can take to reduce your risk of developing cancer.

Such measures include avoiding tobacco products, keeping a healthy weight, staying active throughout life, and eating a healthful diet, all of which may reduce a person’s lifetime risk of developing cancer. These same behaviors are also associated with a lower risk of developing heart disease and diabetes.

Although we all have the ability to make healthy choices, the social, physical, and economic environments in which we live may positively or negatively impact our ability to “stick with” our well-intended plans. Nevertheless, is it important to realize that you are in control.4

Targeted monitoring

Personalized medicine introduces the ability to use markers that may signal risk or detect disease before symptoms appear. Women with certain BRCA gene variations have an increased risk of developing breast cancer.

Increasing the frequency of mammograms may be recommended to help early detection, or preventive surgery or chemoprevention may be considered for possible risk reduction. Genetic markers are also currently being used to facilitate safer and more effective drug dosing and scheduling.3

Diagnosis

Fulfilling the promise of personalized medicine requires that these findings be translated into precise diagnostic tests and targeted therapies.

In current practice, cancer diagnosis is primarily based on symptoms (clinical presentation) and by your pathology report. New molecular tools may help to characterize cancer subtypes that cannot currently be distinguished clinically and may provide predictive information concerning disease outcome, aiding in guiding treatment decisions.

Below are types of testing now being used to provide your doctors with the information they need to make an accurate diagnosis of your cancer type and stage.

Hereditary Gene Testing

Personalized medicine is being used today in the testing of inherited genetic mutations. For example, specific BRCA1 and BRCA2 gene mutations are implicated in familial breast and ovarian cancer. Genetic testing can be provided to determine individuals at increased cancer risk due to such BRCA mutations, which may prompt more intense monitoring and consideration of prophylactic therapy.

Somatic Gene Testing

Personalized medicine is now being used to detect “somatic” or non-inherited mutations in cancer. Somatic mutations refer to acquired gene mutations or DNA changes that occur after conception. Some examples are the following:

• Mutations of the KRAS gene in advanced colorectal cancer are predictive of a poor response to therapy with anti-EGFR (anti-epidermal growth factor antibody) agents, an important finding that now guides treatment decisions for patients with and without KRAS mutations
• The discovery of a chromosomal translocation in chronic myelogenous leukemia (CML), led to the development of a new drug called Gleevac that targets the enzyme produced as a result of that mutation.

Diagnostic testing – a few examples

• Oncotype DX is a diagnostic test to detect patterns of genetic abnormalities within tumors. These patterns predict the probable rate of recurrence and can help guide treatment decisions. This test is available for both breast and colon cancers.
  For more information on this click here.
• Testing for the overexpression of Her2 gives physicians information to make
  treatment recommendations. For more information on this click here.
• Testing for estrogen and progesterone status also helps determine
  treatment recommendations. For more information on this click here.

Therapy

New molecular tools may also provide doctors with information on which drugs their patients may or may not respond to and/or the likelihood of their developing adverse effects associated with certain agents.

Targeted Therapy

Targeted therapy is the use of agents designed to target specific mutated molecular pathways in a subset of patients with a given cancer type.

• As noted earlier, trastuzumab (Herceptin®) and additional anti-HER2 agents may be used to treat patients with HER-2-neu positive breast cancer and cancers of the stomach and gastroesophageal junction.
• Also mentioned earlier, imatinib (Gleevec®) is used to treat chronic myeloid leukemia that has the Philadelphia chromosome.
• Using a whole genome screen to identify genes active in cutaneous T-cell lymphoma (CTCL), scientists found that presence of the protein HR23B predicted response to the drug vorinostat (Zolinza®).
• 5-fluorouracil (5-FU) is a commonly used chemotherapy agent. Dihydropyrimidine dehydrogenase (DPD) is the primary enzyme that determines the breakdown of 5-FU. Some people have genetic variations, causing the DPD enzyme to be less active or inactive, limiting the metabolism of 5-FU.

As a result, people with such DPD mutations have a higher risk of developing severe or even fatal reactions to 5-FU. Screening for DPD mutation and direct measurement of DPD activity prior to treatment with 5-FU will enable proper adjustment of dosage to prevent a dangerous adverse reaction.

Response Monitoring

To truly wipe out cancer cells within the body, it is not enough to have effective drugs that target some of the cancer growth pathways. It is important to have a way of monitoring the cancer itself, so that drug therapy can be adjusted should the tumor change or evolve. Response monitoring may be done by measuring tumor markers (biomarkers).

“Content Developed September 1, 2012”