Precision medicine describes an approach to treatment based on an individual patient’s unique genetic, environmental, and lifestyle factors. Genetic data, in particular, is central to the concept of precision medicine.
Perhaps more so than with any other disease state, precision medicine has had a definitive impact on the treatment of cancer. With the approval of imatinib (Gleevec®) to treat chronic myeloid leukemia (CML) nearly two decades ago, the concept of treating cancer based on underlying genetic anomalies was launched. In the case of CML, the underlying genetic abnormality is central to the diagnosis of the disease, but this is not the case for many other types of cancer. Specific genetic mutations may or may not be present in different patients with the same type of cancer. Identification of specific genetic mutations within cancer cells has led to the development and United States Food and Drug Administration approval of approximately 30 different “targeted” cancer treatments.
Tissue from the patient’s tumor is considered the gold standard for establishing the diagnosis and for identifying potential precision medicine targets. However, several challenges are associated with obtaining and interpreting information from tumor biopsies. Tumors may be located in areas of the body that are difficult to access and may require invasive procedures in order to obtain the needed tissue.
The use of liquid biopsies in place of tumor tissue biopsies is an emerging technology that may help to accelerate the use of precision medicine. The term liquid biopsy most commonly refers to the detection of tumor DNA fragments in the patient’s blood. This circulating tumor DNA (ctDNA) is the result of a dying cancer cell releasing fragments of DNA into the bloodstream. In addition to blood, liquid biopsies may also have utility with other bodily fluids, including urine, cerebrospinal fluid, and saliva, for example.
Liquid biopsies represent the potential for an easily retrievable source of information about a tumor’s genomic makeup, and they may have other advantages as well. Traditional tumor biopsies are often done on a single tumor lesion, which may inadvertently lead to sampling bias that does not capture the heterogeneity found in many tumors and/or different metastatic sites of the tumor. Conversely, ctDNA may provide a better “big picture” of the overall genetic makeup of the tumor cells. Another potential utility for liquid biopsies is the improved ability to monitor changes in the tumor’s genetic profile over time. Serial liquid biopsies can detect when a tumor acquires resistance to the current therapy before other manifestations of tumor progression are established. Liquid biopsies may also be able to spare patients more intensive treatments that offer limited added benefit. For example, in some types of cancers, the detection of microscopic residual disease remaining after surgery may identify patients who will benefit from further systemic therapy. Conversely, patients without this detectable residual disease by ctDNA may be spared from further toxic therapy that would not increase their chance of cure. TPerhaps the most hopeful use of ctDNA technology is the ability to screen and identify asymptomatic patients who are at a very early stage of their cancer when the possibility for cure is much higher.
For now, tumor tissue biopsies remain the standard of care in the majority of clinical situations; however, if the promise of liquid biopsies is validated through further study, more patients may be able to benefit from the promise of precision medicine.
