Advances in Genomic Lab Services Drive Patient-Centered Clinical Trials
How can clinical trial sponsors employ genomic data insights to propel patient-centered drug discovery and development?
David Latto, PhD, is the director of Science Liaison Genomics at Q2 Solutions, a clinical laboratory services organization. Latto has more than 25 years of experience in the biomarker and precision medicine space and has earned his PhD in human molecular genetics from the University of Cambridge.
From drug discovery and development to precision medicine, advances in genomics are supporting pharmaceutical and biotech companies to delve deeper into cellular-level insights to offer personalized treatments and patient-centered clinical trials. Whether it’s for insights into tumor mutational profiles, drug mechanisms, signaling pathway changes, cell-state or population changes, or rapid turnaround sample testing, here are a few examples to demonstrate the impact of genomic lab services on clinical research.
Single-cell sequencing
Single-cell sequencing is being increasingly adopted into drug development and clinical trials to understand targeted, molecular-level responses across specific cell types. With this technology, researchers can analyze:
- Sample heterogeneity
- Molecular differences among cell types to identify cell populations of interest (e.g., tumor cells, certain immune cells)
- Gene expression pattern and signaling pathway changes in individual cells and cell types
Following are some recent innovations in single-cell sequencing.
FFPE and fixed cell sample analysis
Traditional single-cell sequencing analysis requires fresh cell suspensions or tissue sections. But patient tissue samples from clinical trials are typically available as “fixed” samples (i.e., formalin-fixed, paraffin-embedded blocks/slides), a sample type incompatible with single-cell analysis.
With recent technological platform innovations, a few expert labs are now able to use fixed tissue samples for single-cell sequencing to gain multidimensional insights across thousands of cells per sample. This technology allows an in-depth understanding of tumor cell and immune cell populations and also aids in designing targeted immunotherapies.
Gene expression
The ability to explore gene expression in individual cells can be tremendously valuable to trial sponsors who want to gauge multilayered changes in cellular networks, including:
- the impact of disease on the state and variation within a tissue and/or immune cell types,
- the impact of therapy on different immune cell populations and/or their cell states, and
- a therapy’s mode of action in specific cell types through changes in gene expression signatures and cell signaling pathways.
These insights help sponsors determine the inner workings of a cell, gauge whether their therapy’s mechanism works as designed, and potentially secure additional useful findings to guide strategies. For example, T-cell or B-cell receptor sequencing can provide insight into clonal changes in the T-cell (or B-cell) population and how they respond to disease or treatment.
Advancing multigene cancer panel analysis
Clinical trial sponsors often invest in multigene cancer panels that can screen and analyze relevant cancer biomarkers in tumor samples or circulating tumor DNA in liquid biopsy.
Large panel assays
Latest solutions employ a hybrid-capture approach to target cancer-related genes using liquid biopsy instead of solid tumor samples, as the latter are less accessible and an inconvenience to the patients. Techniques such as the hybrid-capture approach enable high-quality and reliable biomarker detection in a patient-friendly manner.
Trial sponsors are preferring commercially available, comprehensive, large multigene panels over individual biomarker assays. Innovative large-panel assay solutions can help examine approximately 500 genes with one test to identify key variants relevant to a range of solid tumor types and measure complex markers, such as tumor mutational burden and microsatellite instability.
Precision-focused panels
Targeted multigene panels are commercially available for profiling RNA and DNA biomarkers across 50 genes from solid tumor and liquid biopsy samples. Small panels focus on the most common solid tumor types and mutations. Depending on the platform technology used, they may work well on smaller sample sizes and shorten the testing turnaround times for cancer diagnosis and therapeutic decision-making.
Through these genomics lab innovations, trial sponsors can strengthen research and development programs to yield deeper molecular insights. Approaches and assay choices can be tailored to suit program requirements—bulk or single-cell sequencing analysis; liquid biopsy or solid tumor profiling—to gather accurate evidence and better meet patient needs.