dPCR and Effective Use of Liquid Biopsy in Cancer Diagnosis
The spotlight on liquid biopsy is getting brighter. Technologies such as next generation sequencing (NGS) and digital PCR (dPCR) combined with the continual quest of cancer researchers like Dr. Atocha Romero are allowing us to determine potentially effective use of liquid biopsy in cancer diagnosis and management.
Atocha heads the Liquid Biopsy Laboratory (LBL) at Hospital Universitario Puerta de Hierro in Madrid, Spain. Her lab focuses on biomarker discovery and performs liquid-biopsy-based non-invasive biomarker testing for subjects with lung and other cancers.
Our Senior Marketing Manager, Dr. Deepak Tripathi, interviewed Atocha to learn about the challenges she faces in the field and how she attempts to solve them.
Conversation with Dr. Atocha Romero
Q: You have been working in the translational cancer field for a very long time. What motivates you to fight cancer? Why did you choose oncology research?
A: Cancer is very prevalent, so I was always interested in fighting against it. As a pharmacist, I wanted to study molecular biology as it is very relevant in the oncology field.
The development of targeted therapies has significantly improved survival in patients, mostly due to advances in molecular biology. I see its positive impact on patients every day. This pushes us to keep going.
Q: What questions are you trying to answer with your research?
A: We are trying to analyze the clinical utility of liquid biopsy in cancer, mostly for lung cancer patients. Liquid biopsy is useful for non-invasive biomarker testing, especially in patients with lung cancer because lung cancer tissue is difficult to access.
Besides, lung cancer is often diagnosed at an advanced age. Therefore, we want to know if liquid biopsy can be used to monitor disease and guide clinical decision-making.
We are also exploring the clinical utility of liquid biopsy in the context of neoadjuvant clinical trials. Neoadjuvant therapies are given to patients before they go into surgery. We are asking if we can use liquid biopsy to evaluate the efficacy of neoadjuvant treatments. This is very important because we need early endpoints that correlate with long-term survival and that can be measured faster than overall survival. This way we can speed up the process of such clinical trials.
Q: What challenges do you face in delivering patient care in translational medicine and how have Applied Biosystems technologies helped you?
A: One of the challenges we face is the incorporation of NGS in the clinical setting. In Spain, it’s taking a while to incorporate NGS for the diagnosis of cancer patients, but we need to go for it. One of the reasons for this delay could be that many pathologists are not yet used to such technologies.
I believe more information in the form of educational webinars and events from Applied Biosystems could help them incorporate new technologies and ways of analysis for the management of cancer patients within clinical research.
Q: What are the benefits of using qPCR and dPCR in translational cancer research over NGS and other technologies?
A: NGS has proved itself as a very useful technology for biomarker testing in solid tumor biopsy. It is recommended, particularly for lung cancer patients, where there are a lot of targeted therapies available.
Digital PCR is very useful to monitor disease progression. We use dPCR to monitor mutations. For example, when the tumor of a patient has a druggable mutation, monitoring that mutation over the course of the treatment is very helpful because, together with the imaging information, dPCR monitoring enables us to narrow down strategies for patient management.
Also, dPCR is cheaper than NGS. In our institution, we can get it done for less than 15 Euros per sample. It’s very informative and enables more accurate management of patients that participate in our studies.
Q: What are your thoughts on using multi-omics approaches to identify new targets and biomarkers, especially while dealing with more procedure-oriented treatments?
A: I believe multi-omics approaches are going to improve the diagnosis of cancer patients, especially in lung cancer where there are a lot of approved and upcoming targeted therapies.
Multi-omics approaches enable more efficient management of tissue samples, thereby opening up more possibilities for the treatment of patients.
Q: To what extent does liquid biopsy compliment radiographic imaging in the detection of early recurrence of definitively treated lung cancer? What is your opinion as an expert in liquid biopsy?
A: Liquid biopsy can complement imaging data. So sometimes there is inflammation surrounding the tumor and that would be a confounding factor because you may think the tumor is growing, where it is not. So in this case, liquid biopsy can help.
Also, during screening, combining information from liquid biopsy with imaging data can help reduce false positives. This way we can avoid unnecessary invasive follow-up biopsies.
Q: Any thoughts on tumor mutational burden (TMB) and microsatellite instability (MSI) in blood as biomarkers for immunotherapy?
A: TMB is a promising predictive biomarker for immunotherapy. The challenge we face with TMB is clonal hematopoiesis.
Clonal hematopoiesis refers to non-malignant mutations in blood cells. It becomes frequent with age. So, as we get older, we accumulate mutations, also in blood cells, which can interfere with using TMB as a biomarker. Therefore, we need mechanisms to filter out mutations from clonal hematopoiesis to accurately estimate TMB in blood.
Q: Which molecular targets are of particular interest to you?
A: We focus on molecular targets with approved therapies, such as EGFR and ALK. We do intense research in ALK testing using liquid biopsies because patients with ALK rearrangements are more difficult to detect than a SNP and we are researching on which way yields better results and higher positivity rate using liquid biopsy to test this alteration for these patients.
Q: What is your message to early-career young scientists who are starting their journey in the research field?
A: My recommendation to young scientists is that they should follow what they like and pursue their goals. Science is sometimes difficult, but in the end, you will get the results if you don’t give up. So, do not give up on your dreams!
— This interview has been edited for length and clarity.
Learn More About dPCR and Other Advanced Technologies for Cancer Research
» Applied Biosystems Solutions for Cancer Research
OncoDxRx Focused on Building an One-Of-A-Kind Liquid Biopsy Theranostic Capability
OncoDxRx, which is using its multiple one-of-a-kind liquid biopsy technologies to speed up precision medicine, is seeking for investment and partnership. The scientists expressed their company with the expertise, knowhow and dynamism of stereotypical high-tech startup.
According to the company, PGA (Patient-derived Gene expression-informed Anti-cancer drug efficacy) technology is the “game changer” because precision medicine currently only benefits 20-30% cancer patients. “PGA, on the other hand, targets this 70-80% population whose biomarker testing are negative, hence completing the puzzle and benefiting the entire cancer population,” the company said.
OncoDxRx also is now developing multi-cancer early detection (MCED) and minimal residual disease (MRD) tests, both of which leveraging on exclusive cell-free DNA methylation and mRNA profiling technologies with huge market demands worldwide.
The company has remarkably outgrown its current pipelines to cover all stages of cancer from early detection, treatment selection, monitoring, recurrence to therapeutics discovery.
OncoDxRx’s role as a driver of precision medicine is a result of being thinking outside of the box and realization of what patients are truly needed most.
The DNA repair activity measurement is another breakthrough that can be used to quantify DNA repair function, either HRR (homologous recombination repair) or MMR (mismatch repair), in circulation without the labor-intensive, time-consuming and costly sequencing or multimodal testing. According to OncoDxRx, the technology has robust chemistry and benefits from high throughput, automation and quick turnaround.
Unlike OncoDxRx, many biotech and clinical laboratory startups appear to be service companies. “Our business model is making revenue and validating exclusive technologies we can sell as fast as possible, as we don’t have the same possibilities as the big players.” The company noted.
“As reputations die hard, and we’re a small company in a big world—we have to reach out to be seen.” The company concluded.
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