As 2020 approaches, it is fair to say that significant—and perhaps surprising—advances will be made in the precision medicine and omics arenas, as there were in 2019.
While we don’t know for sure what lies ahead for 2020, six industry leaders have shared with Clinical OMICs and now you, our readers, their vision for what may lie ahead in the coming year and their implications. Last year, the predictions leaned heavily on advances on data handling, ownership, and privacy protection. This year, there are no common themes, with predictions touching on advances in cancer diagnostics, liquid biopsy, rare disease diagnosis, and single-cell analysis, among others.
The Single-Cell Revolution is Just Starting, and Spatial is the Next Frontier
Over the past few years, the single-cell revolution has begun, but it is just getting started. 2020 will bring a continued expansion of single-cell applications, especially in the areas of oncology and immunology, as well as multi-omics method development. Additionally, we will also see the emergence of commercial platforms for spatial transcriptomics.
Further, these different modalities will become more integrated, providing new forms of multi-dimensional data that will transform our understanding of human disease.
Global scale initiatives like the The Human Cell Atlas will continue to generate new foundational knowledge about the biology of disease. These discoveries will transform our prior understanding of disease mechanisms and, in turn, lead to new approaches for drug and diagnostic development.
The immune system is one of the most dynamic and complex systems in the human body. Throughout 2020, our understanding of the underlying mechanisms of innate and adaptive immunity will continue to accelerate. In particular, innovations in research techniques like antigen mapping, B- and T-cell receptor sequencing, multi-omics and spatial analysis will drive these new discoveries forward. As a result, scientists will learn how to harness these mechanisms to help combat disease, but also how imbalances can lead to autoimmune disorders.
Finally, next year will see the emergence of spatial genomics. Commercial platforms for spatially-resolved, massively-parallel analysis will become readily available, enabling researchers to add the “where” to the “what” in their research. The next frontier will be to integrate emerging technologies for spatial with single cell analysis in order to create multi-dimensional ways to understand human biology.
The novel technologies and insights we will see in 2020, and beyond, will together accelerate the mastery of complex biology to advance human health.
Genomics Will Become Commonplace
Here in the UK, our biggest change will be felt by patients referred to NHS England’s Genomic Medicine Service. 2020 will see the service fully operational, delivering actionable results to patients. This will have a knock-on effect as genomic tests now have a clear path into routine healthcare.
Liquid biopsies and tracking of ctDNA will continue to engaging in a pioneering ctDNA pilot study for some time now. 2020 should see us deliver our results and recommendations for clinical consideration. With NHS actively engaged in integration of new technologies, our regulators will also be looking to match the pace.
Between the arrival of a genomic test directory in the NHS and steady investment in genomics by industry, the U.K. is very well placed to innovate. Translating that innovation into improved healthcare outcomes is going to require an equally innovative regulatory environment. In that respect, we are lucky to have such a forward-thinking regulator in the MHRA here. A 2020 prediction may well be that regulators around the world follow the lead of the MHRA in not just protecting citizens but actively seeking to improve their lives.
As a final prediction, I expect some positive stories around investment in U.K. life sciences companies. The government is supporting this sector and encouraging innovation and export of innovation like never before. The biggest indicator of the UK turning into a hotbed of genomic innovation is the growing number of incubators and accelerators. That Illumina chose the UK as the base for their second accelerator speaks volumes.
To summarize, 2020 is the year that we no longer talk about genomics going ‘mainstream’, but the year that genomics becomes commonplace. As a result, we will see a boom of innovation from technologies, regulators, and business opportunities, all of which will help improve patient outcomes and quality of life.
The Liquid Biopsy Revolution
Earlier in my career, I labored to optimize CT-guided biopsies, tissue handling, laser-capture microdissection, and nucleic acid isolation and amplification in order to get critical molecular insights into patient tumors.
These experiences fuel my enthusiasm for liquid biopsies, which have the potential to provide ready access to the same molecular data. Simple blood samples may soon help us detect cancer and molecularly characterize a tumor in order to determine its aggressiveness, assess treatment efficacy, optimize overall disease management, and thereby improve outcomes.
As our understanding of cell-free RNA, circulating tumor cells, and exosomes increase, liquid biopsy-based assays will provide increasingly vivid molecular portraits of each patient’s cancer.
While cell-free DNA (cfDNA) is now being assayed to identify cancer-driving variants and guide therapy, that role is expanding. Soon, cfDNA will help determine recurrence risk, detect recurrence earlier than radiology, and inform combination or sequential therapies that will control disease and eventually may provide a path to a cure for advanced cancers.
Our focus on targetable variants will broaden to include patterns of variants and genome-wide signatures, such as those for homologous DNA repair deficiencies. Broader tumor sequencing will show how mutations vary in different tumor microclimates. Future efforts may also incorporate epigenetic markers to understand each cancer’s tissue of origin, metastasis location, or additional phenotypic information.
Single-cell analyses will help us dive into clonal heterogeneity, identifying distribution of variants across the polyclonal population, and provide a better understanding of key cancer-driving mutations. These approaches will help identify the variants, i.e. neoepitopes, that are present across most clones and provide a means to design highly effective bespoke immunotherapies.
Additionally, liquid biopsies will evolve from single-sample analyses that measure a fixed point in a cancer’s progression, to longitudinal diagnostics that track cancer over time.
These approaches will provide invaluable insights into each patient’s unique disease and allow clinicians to stay in front of cancer to control or, some day, cure a patient’s disease.
Rapid WGS, Better Long Read Data, Infectious Disease Testing to Advance in 2020
In clinical genomics, 2019 has been dominated by continuous double-digit growth in NIPT testing and DTC companies announcing plans to move into health testing again.
In 2020, we expect to see various initiatives presenting clinical results on NICU/PICU testing pioneered by Dr. Stephen Kingsmore and his team at Rady’s Children Hospital. Rapid WGS has been accelerating and I expect at least 10 additional urgentcare units in the US and potentially another five international programs to support critically ill newborn babies and kids. EHR integration, further AI-based automation, and moving into routine testing are hot topics in this arena. In addition, we will see the first clinical results returned to All of US participants, a big milestone for the NIH funded effort. To truly generate enthusiasm and drive participation, clinically meaningful information needs to be returned.
With respect to data quality, we should see early studies showing quantitative improvements in diagnostic yield for exomes and genomes applying long-read technology from PacBio, 10x Genomics, and others to the field of rare disease. These will include copy number and structural variants, which are suspected to account for 5% to 10% of missed diagnoses.
While hereditary and somatic testing have followed NIPT testing, I believe the next clinical wave will be WGS testing in infectious diseases. The field of hypophysis-free infectious disease testing has been years behind. But now, algorithms, workflows, and quality control systems are becoming more standardized and established. These results should be exciting in the value delivered to the clinical workflow for vulnerable populations such as newborns, immune compromised cancer and autoimmune patients.
Sequencing and Gene Editing Technology Adoption Will Increase Worldwide
Karen E. Weck
President-elect of Association for Molecular Pathology, Director of molecular genetics laboratory
at McLendon Clinical Laboratories, UNC Medical Center
Over the past several years, we have seen significant technological advances in molecular diagnostics that have helped transform our ability to detect, monitor, and treat cancer and other complex diseases. In 2020, I predict the following innovative technologies will continue to evolve, improve, and be adopted by more clinical laboratories around the world to advance patient care:
- Use of large-scale genomic analysis to drive therapy decisions, including determination of microsatellite instability and tumor mutational burden for immunotherapies
- Use of exome and whole-genome sequencing for genetic diagnosis of multigenic disorders
- Use of plasma analysis for detection of circulating tumor DNA
- Use of CRISPR technology for molecular diagnostic and therapeutic applications
- Use of NGS and phylogenetic analysis to characterize the organisms important for infectious diseases and the normal human microbiome
- Use of clinical sequencing interpretation tools to categorize disease-causing pathogenic variants and normal human
AMP members are among the early adopters of molecular diagnostic testing in clinical settings, and we are committed to continuously improving professional practice and patient care through education, innovation, and advocacy. We will continue to develop and update consensus, evidence-based recommendations to aid clinical laboratory professionals as new data and/or reference materials become available. We will also continue to advocate for adequate insurance reimbursement, coverage, and appropriate regulatory oversight of complex molecular assays.
One of our top priorities next year will be the recent proposal to amend Section 101 of the Patent Act. We will continue to engage key stakeholders to make sure this proposed legislation related to the eligibility of DNA sequences to be patented does not overturn 150 years of patent case law, prevent the development of life-saving diagnostics for devastating diseases, and significantly limit access to optimal patient care.
2020 Will Be a Tipping Point for More Advanced Cancer Patients to Realize the Benefits of Precision Medicine
Precision medicine has reached an inflection point. Personalized cancer treatment is a possibility for more patients than ever thanks to the advent of targeted therapies. With a growing number of new treatment options—including two pan-tumor approvals—the need for broad molecular diagnostic tools to match patients with these therapies has never been greater. We continue to advance our understanding of cancer as a disease of the genome—one in which treatment decisions can be informed by insight into the genomic changes that contribute to each patient’s unique cancer. This shift is already shaping the way biopharma companies develop breakthrough targeted medicines, but now we need to ensure genomic testing is embedded in routine cancer care so that patients can be matched to these treatments.
Despite this progress, as many as 60% of advanced cancer patients are currently not receiving any form of genomic testing. All cancer patients deserve access to information about their cancer so their physicians can make the most informed decisions possible. In 2020, I believe the 60% statistic will shrink, as we see more patients and physicians seek genomic testing to inform personalized treatment options. We will see comprehensive genomic testing become more widely utilized, with the eventual goal of these tests becoming the standard of care for all patients with advanced cancer at diagnosis. Whether it’s a solid tumor test or a liquid biopsy, these tools are helping make precision medicine a reality for many.
With so much hard work under our collective belts, it is my prediction—and hope—that 2020 will see a sizable shift in the number of cancer patients who benefit from truly personalized care.