Biomarker Testing, Explained
Ever wondered what biomarker testing really refers to and what it means for your treatment options? Read on for a simplified explanation of how biomarkers can drive cancer, how testing is done, and how they can affect treatment decisions. Bonus section: an unusual case study where a patient achieved partial remission by re-using Brigatinib after progression on Lorlatinib. This case study demonstrates that rechallenging with a previous TKI should not be ruled out as a valuable treatment option in some cases.
Biomarker Testing Simplified:
A biomarker is any molecule that can be measured in blood, other bodily fluids, or tissue. Many have heard of genetic markers, biomarkers, or genotypes. This is genetic information for doctors to understand the specific type of tumor that each patient can have.
ALK is a change in the patient’s own cells that lead to their uncontrolled growth. These types of mutations are called “driver mutations” because the change prompts an increase in the activity of a protein, much like driving a car without a brake. A fusion or rearrangement can happen if a gene is fused to another and the “brake” is lost. Amplification mutation means that there are too many copies of the same gene leading to uncontrolled activity. A third type of a driver mutation is a deletion mutation, where the brake pedal of the car is yanked out. There are over 20 different driver mutations known for non-small cell lung cancer to date.
Because we know what driver mutations can occur in adenocarcinoma lung cancer, using techniques to screen for known biomarkers is a good starting point for patients. Samples of the tumor or biopsies can be obtained via bronchoscopy, endobronchial ultrasound-guided transbroncial needle aspiration (EBUS-TBNA), transthoracic needle biopsy, thoracoscopy, or thoracentesis. An additional biopsy may be performed during treatment in case of tumor progression.
In addition to tissue biopsy, liquid biopsy can be used to measure some biomarkers. As the name implies, a liquid (in this case blood) is used as the medium to test for biomarker signatures. Tumor cells can leave traces of themselves (called circulating tumor DNA or ctDNA) in the blood. Scientists have devised very sensitive tests to find the few ctDNA in the bloodstream. However, it is important to understand that ctDNA quantity is very low, so one cannot exclude the existence of a mutation if it is not detected by liquid biopsy.
What does “actionable” mean? In the case of biomarkers, actionable means there are current treatment options available. There are more biomarkers that can be tested for than medicines available for each subtype of biomarker/mutation. Why then test for biomarkers that are not actionable? There are benefits to finding non-actionable biomarkers because there might be clinical trials specific to some of those, as well as new trials that may be developed in the future.