Translating New Noninvasive Screening Methodologies to Clinical Practice

Honey Reddi, PhD, FACMG, served as a professor and chief of the Division of Clinical Genomics at the Medical College of Wisconsin before joining Belay Diagnostics LLC, IL, as senior vice president and medical director. Her research interests include cancer biology, viro-therapeutics, and genetics of somatic and inherited disorders.

What recent advances in clinical screening technologies and biomarker research show promise?

Noninvasive screening technology, such as liquid biopsies, has made significant advances in the field of oncology Liquid biopsy is a good way to screen for cancers that are difficult to biopsy, for example, lung cancers and brain tumors, or whose tumor sample has been exhausted. If a patient has had resections, liquid biopsy is a great noninvasive monitoring tool. Liquid biopsies definitely have a range of applications and unexplored potential.

In one of my previous laboratories, we developed a plasma monitor assay that screens for a set of 14 genes (PMID: 30745794). We are working on liquid biopsy for central nervous system tumors in my current laboratory. Early detection using epigenetics and epigenomics is an area of active research.

In breast cancer research, for instance, scientists are using homologous recombination markers for early detection of cancer and exploring associated epigenetic changes. DNA methylation is another key biomarker that has caught a lot of attention.

What protocols are in place to standardize and validate clinical biomarkers?

The industry is always looking to bring in new assays and lab-developed tests (LDTs), which are largely protected by intellectual property law. With the upcoming FDA regulation of LDTs, some labs will work to get approval for their LDTs, aiding in reimbursement and revenue generation. 

However, concerns about the impact of FDA oversight of LDTs have led experts part of professional societies like the Association for Molecular Pathology and the American College of Medical Genetics to advocate for the status quo. 

Even so, everybody is actively working toward validating and standardizing biomarkers and LDTs, while keeping in mind that the FDA may potentially take over.

As a clinical geneticist, what screening technologies are you currently using?

When I started my career in research, we used PCR and Sanger sequencing. We made all the required components, enormous gels, etc. By the time I finished my PhD in 2000, we’d moved to using pre-made kits. The field has progressed very quickly in the last 20 years—now, everything is automated, and in the last decade, next-generation sequencing has taken over. Today, short- and long-read sequencing is being used across most clinical labs and research laboratories respectively. 

From a clinical genetics and diagnostics perspective, microarrays were the first choice for diagnosing inherited disorders. But newer techniques, like optical genome mapping, can now detect structural variants that microarrays couldn’t. Digital droplet PCR (ddPCR) is another technique that yields a significant level of quantification with higher sensitivity; ddPCR is particularly helpful in detecting rare variants with lower allele frequency variance.

The clinical diagnostics field is rapidly evolving and keeping up with it can be a challenge. Networking and continuing education, such as at scientific conferences, ensures the professional community remains up to date with the latest advancements. However, it is equally important that the next generation of laboratory professionals be trained and have access to these new technologies.

What factors ensure screening methods translate successfully into mainstream clinical practice?

Firstly, productive collaboration. People who have developed a method should be open to collaborating with other labs to successfully launch it in a clinical setting. Besides monetary investment, researcher(s) must be invested in a product, and understand and believe in its value. Insightful leadership is another factor. Ensuring a product leaves the research lab and is successfully implemented in clinics requires foresight, vision, and positive team dynamics. Having the right people makes a significant difference. Above all, investing in cross-training your staff and focusing on their success and growth is vital to ensure high-quality patient care.