Cancer biomarkers are biological molecules that are produced by the tumor or by other cells in the body as a response to the tumor. Biomarkers can typically differentiate a person with cancer from a person not affected by the disease. Biomarkers can be found in the tumor tissue, blood or other body fluids. The types of different cancer biomarkers include mutations in genes, extra copies of genes, gene rearrangements, abnormal expression of proteins and metabolic byproducts. Some biomarkers can be inherited from a parent as a risk factor for developing cancer during the lifetime of a patient while other biomarkers are derived directly from the tumor. Every cancer is different and as such detection of biomarkers in cancer will help facilitate a personalized treatment plan for the patient.
Clinical Use of Biomarkers
Biomarkers can be classified into the categories below based on their clinical utility.
- Predictive biomarkers – These biomarkers predict response to a therapy. A breast cancer patient with extra copies of the HER2 gene will respond favorably to the HER2 inhibitor Trastuzumab. A colorectal cancer patient with a KRAS mutation will not respond to cetuximab and will be resistant to the drug. As such, predictive biomarkers help determine which therapies will be most effective.
- Prognostic biomarkers – Biomarkers that predict patient outcome. FLT3 mutation in acute myeloid leukemia predicts poor clinical outcome.
- Diagnostic biomarkers – Biomarkers that helps clinicians to accurately identify a subtype of cancer. EWSR-FLI1 gene fusion is seen in all Ewing’s sarcoma patients and help differentiate this subtype of the disease from other sarcomas.
- Risk assessment biomarkers – Biomarkers that predicts the patient’s risk of developing a malignancy. Pathogenic mutations in BRCA1 and BRCA2 is a risk factor for developing breast and ovarian cancer.
- Cancer recurrence monitoring biomarkers – Biomarkers that is used as a surveillance marker to monitor recurrence of cancer. High levels of CEA in colorectal cancer indicates cancer relapse.
Biomarker use in Clinical Trials
Oncology clinical trials are increasingly using biomarkers in the stratification of patients and to identify patients that may respond favorably to an investigative drug. BCR-ABL in leukemia and HER2 in breast cancer were two of the earliest biomarkers that were used to identify targeted therapy in cancer. The last decade or so has seen an exponential increase in FDA approvals for biomarker based targeted therapy including novel markers such as IDH1, IDH2, and NTRK. In addition, there are promising interventions in late stage clinical trials including MET inhibitors for MET exon 14 mutated lung cancer and FGFR inhibitors for FGFR altered breast cancer.
Screening for Cancer Biomarkers
Screening for biomarkers has facilitated the early detection of cancer. Biomarker tests can be a single gene test such as testing for EGFR in lung cancer, a cancer type specific panel testing for 20-30 genes or a comprehensive gene panel such as the FDA approved FoundationOne test for 100s of genes for solid tumors. If you have a family history of cancer, speak to your physician or genetic counsellor about testing for susceptibility of cancer. This is especially important if you have a close family member with breast cancer or early on-set colorectal cancer. Biomarker testing is also warranted when the cancer patient does not respond to frontline chemotherapy and treatment options have been exhausted.