How liquid biopsies are rewriting the playbook for cancer diagnosis and treatment
For many, cancer is a death sentence, or at least feels like it. The success of cancer treatment and the patient’s prognosis is highly dependent on how early it gets detected and if the correct therapeutic interventions are applied. Too often patients go undiagnosed until late stage disease, where metastasis may have occurred and treatment options are limited, or commit to a treatment plan, only for doctors to realize it never would have worked.
So what are researchers and clinicians doing to combat this situation? Liquid biopsies.
What are liquid biopsies?
A liquid biopsy is a relatively non-invasive technique for detecting and analyzing tumors by using biomarkers circulating in fluids such as blood, saliva, and urine. These biomarkers can include circulating tumor cells (CTC), circulating tumor DNA (ctDNA), microRNA, exosomes, proteins, and other biomolecules shed by the tumor or within the tumor microenvironment.
Liquid biopsies are rapid and reproducible, and are proving to be high-impact for a variety of reasons:
Earlier detection and frequent monitoring of cancer
They could be a reasonable alternative to tissue biopsy, particularly for difficult-to-extract samples (e.g., brain) to diagnose tumors and determine the stage of metastatic lesions. This can help avoid complications that occur after invasive biopsies (e.g., bleeding, infections, and pain).
Because it is rapid, reproducible, and minimally invasive, a patient can be monitored over the course of treatment, providing early warnings of recurrence and the ability to predict cancer in “healthy” people before symptoms appear.
Example: CancerSEEK is a highly accurate blood-based assay that hunts for tumor DNA and protein biomarkers to detect ovarian and liver cancers.
Guiding cancer treatment decisions
With advances in genomic-analysis, scientists can detect a mutation known to cause resistance to a particular drug, which may have gone undetected in the tissue biopsy. With tissue biopsies, your data is only as good as where your needle was placed. Liquid biopsies offer researchers and clinicians another chance at detecting genetic markers, enabling them to forecast the response or resistance to certain drugs.
Example: The TACTIK clinical trial is using the number of CTCs to define when resistance to chemotherapy appears in people with metastatic, castration-resistant prostate cancer. This can indicate to the oncologist when the therapy needs to change.
Where are we now with liquid biopsies?
Confidence is growing due to numerous studies generating impressive results—for science, clinicians, and patients—but we are lacking preclinical and clinical standardization, keeping the oncologist’s toolbox limited to traditional diagnostics techniques, such as tissue biopsies and imaging.
A few liquid biopsy tests are FDA approved.
- CellSearch is used to detect metastatic prostate, breast and colorectal cancer by using beads coated with antibodies that bind to cell proteins to capture CTCs.
- Guardant360 CDx uses next generation sequencing technology to identify patients with specific EGFR mutations in metastatic non-small cell lung cancer.
- FoundationOne Liquid CDx looks for mutations within 324 genes implicated in cancer.
An abundance of clinical trials and research is devoted to liquid biopsy assay development for wide-ranging cancers, with the goal of complementing current cancer diagnostic and monitoring methods.
What do we need to do to standardize liquid biopsies
To cement liquid biopsies in clinical guidelines, clinical researchers need to overcome several limitations and challenges:
- Generate assays capable of detecting biomarkers at minuscule levels. Circulating tumor molecules are typically lower abundance than non-cancer-related molecules.
- Identify the ideal combination of biomarkers to detect for specific types of cancer.
- Minimize false-positive and false-negative results as both can be detrimental—physically, mentally, and financially—to patients
- Organize and complete large-scale cohort studies to determine the effectiveness and sensitivity of the liquid biopsy.
Overcoming these challenges requires strong collaborations between industry and academia, and will require buy-in from patients. To prove the utility of these biomarkers, the scientific community needs to conduct more early detection and interventional clinical studies and needs an algorithm that can identify the appropriate combination of biomarkers that will paint an accurate picture of the tumor profile.