Jeremiah McDole
Cancer remains a leading cause of death worldwide. However, as cancer treatments continue to improve and diagnoses happen sooner, more and more patients are experiencing remission. To further increase survival rates and reduce unnecessary treatment, scientists and clinicians are turning to ultra-sensitive molecular analysis to inform treatment decisions and predict and detect relapse.
Circulating tumor DNA (ctDNA) can yield an incredible wealth of information about a cancer’s progression, response to treatment, and likelihood of recurrence. However, key biomarkers are often lowly abundant, placing them below the limit of detection of common tools such as quantitative PCR (qPCR). The sensitivity and precision of Droplet Digital PCR (ddPCR) technology give scientists the power to detect and quantify nucleic acids in blood samples for cancer detection and treatment monitoring.
Enhancing Academic Oncology with ddPCR Technology
Hundreds of publications have already demonstrated ddPCR technology’s robust utility in ctDNA analysis and other oncology applications. Since hematological malignancies inherently circulate in the blood, they present an especially natural target for molecular monitoring. In Sweden, clinical researchers used custom ddPCR assays to enable early detection of myelodysplastic syndrome (MDS) relapse, which allowed doctors to intervene earlier and produce better patient outcomes. On the opposite end of the treatment spectrum, the sensitivity of ddPCR methods gave clinicians in the life after stopping tyrosine kinase inhibitors (LAST) study the confidence to declare certain chronic myeloid leukemia (CML) patients were at such low risk of recurrence that they could cease tyrosine kinase inhibitor (TKI) treatments, freeing them from what could otherwise include many years of unpleasant and unnecessary side effects (Atallah et al. 2018).
ddPCR applications are not limited to the study of blood cancers, however. Solid tumors also shed ctDNA that can be detected and analyzed with ddPCR assays. Quantifying changes in ctDNA levels allowed one group of researchers to determine how lung cancer patients were responding to immunotherapy and make clinically relevant predictions based on that information (van der Leest et al. 2021).
Industry Applications of ddPCR Assays
ddPCR technology has provided valuable insights for industry clinical trials, as well as in academic clinical research settings. Biodesix, a data-driven diagnostics company, applies ddPCR assays in multiple areas of clinical oncology research. In some of their studies, ddPCR technology provides a cost-effective method to screen patients non-invasively for specific mutations that make them eligible for a particular clinical trial. Following enrollment, scientists running those clinical trials have used ddPCR assays to track the prevalence of specific mutations over time and monitor patients for resistance mutations that might arise during a certain treatment course. Finally, as in many clinical research studies, ddPCR assays have proven ideal for serial monitoring that allows Biodesix and their collaborators to track disease progression and identify disease recurrence in clinical trial participants.
“As early as three weeks post-treatment, differences in ctDNA levels can offer accurate prognoses,” says Biodesix Chief Development Officer Gary Pestano, PhD. Patients with lower levels of ctDNA demonstrate better outcomes overall — and ddPCR technology provides absolute quantification of those ctDNA levels.
“We expect Droplet Digital PCR applications to extend beyond clinical research and into commercially available translational testing solutions,” says Pestano.
Expanding Possibilities with the QX600 ddPCR System
To unlock even more capabilities for ctDNA sample analysis for translational applications, Bio-Rad recently released the QX600 ddPCR System.* This technology will:
- Deliver more answers per sample — With advanced six-color multiplexing, scientists can clearly discriminate and quantify up to a dozen biomarkers per well. This improves efficiency, conserves resources, and reduces sampling burdens on patients
- Maximize clinical research impact — Access to a platform with ultra-high precision, sensitivity, and reproducibility allows scientists to obtain better data than ever before
- Accomplish more with a single instrument — ddPCR technology is a highly versatile platform that can quantify SNPs and structural variants, characterize methylation, perform RNA expression analysis, and more
- Simplify clinical laboratory logistics — Same-day turnaround time, simple workflows, and intuitive data analysis lower the burden on laboratory teams, reducing the need for specialized training and freeing up time to answer other important scientific questions
When combined with broad screening tools, such as next-generation sequencing (NGS), cutting-edge ddPCR technology is part of an ideal precision medicine workflow. As ddPCR technology advances, clinical researchers and industry experts alike will continue to establish new uses and standards to ultimately deliver more personalized, timely treatments for all cancer types.
* Research use only. Not for use in diagnostic procedures.
References
Atallah E et al. (2018). Design and rationale for the life after stopping tyrosine kinase inhibitors (LAST) study, a prospective, single-group longitudinal study in patients with chronic myeloid leukemia. BMC Cancer 18, 359.
van der Leest P et al. (2021). Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors. Mol Oncol 15, 2910–2922.