Liquid Biopsies: Revolutionizing Non-Invasive Cancer Diagnostics
Liquid biopsies have surged in popularity and importance over the last few years, representing a major advancement in medical diagnostics. Groundbreaking improvements in technology have moved the bar for accuracy and reliability, marking a significant inflection point and market opportunity.
Background
Unlike traditional tissue biopsies, which require invasive procedures to collect tissue samples, liquid biopsies analyze bodily fluids, typically a standard blood draw. The analysis requires highly sensitive assays that can detect small quantities of highly fragmented tumor-derived DNA and RNA found in blood. This allows a standard blood draw to detect biomolecular traces of diseases like cancer. Liquid biopsies have the ability to detect circulating tumor DNA (ctDNA), cell free DNA (cfDNA), circulating tumor cells (CTCs), and other biomolecules that shed from tumor sites into the bloodstream, often while cancer is still at the local and regional stages.
For cancer detection, there are three main applications: early detection and screening, targeted therapy and/or patient trial selection, and minimal residual disease (MRD) or patient monitoring. Of these, early cancer detection is likely to have the largest impact. Numerous companies and clinical trials are focused on liquid biopsies for both single screening and multi-cancer detection (MCED). Catching cancer at the earliest stages helps to reduce healthcare costs and save lives.
The Opportunity
Cancer Prevalence: The rising incidence of cancer has heightened the demand for non-invasive diagnostics, early detection and personalized treatment monitoring. The CDC predicts that by 2050, cancer incident cases will increase 50%.
COVID-19: The pandemic accelerated the need and urgency for less invasive testing and screening methods, as patients and healthcare providers seek safer and lower friction alternatives to traditional biopsies.
Payer Incentives: Insurance plans and payers are starting to recognize the cost-effectiveness and clinical value of liquid biopsies, leading to better coverage and reimbursement. One study estimated the national cost-savings in the United States from early cancer diagnosis at $26B per year. Another study shows MCED testing can decrease the cost of each cancer incident by $5,421.
Precision Medicine: The growth of personalized medicine is dovetailing with the capabilities of liquid biopsies to provide tailored treatment plans based on real-time molecular data. Pharmaceutical companies are focusing on enhancing the efficacy of targeted therapies through liquid biopsies.
The Technologies
Liquid biopsies detect and analyze ctDNA, CTCs, and other biomarkers found in blood and other bodily fluids. The breakthrough technologies can capture critical information about a tumor or cancer's presence, characteristics, and changes over time. Emerging platforms are increasing the efficacy of liquid biopsies, particularly for early detection, and increasing sensitivity and specificity capabilities for both single cancer detection and MCED.
Next-Generation Sequencing (NGS): NGS is high-throughput technology that sequences millions of DNA molecules simultaneously. It is especially useful for detecting low levels of ctDNA, significantly improving sensitivity (higher true positives, lower false negatives).
Digital Polymerase Chain Reaction (dPCR): dPCR is a refinement of the traditional Polymerase Chain Reaction (PCR) technique. It quantifies DNA molecules by partitioning a sample into thousands or millions of individual reactions, improving the sensitivity and specificity (higher true negatives, lower false positives) of cancer and other disease detection.
Methylation: the addition of a methyl group to DNA, aiding in regulating gene expression and detecting early signs of cancer by analyzing changes in circulating cfDNA.
Fragmentomics: analyzes the fragmentation patterns of cfDNA in blood, which allows for examination of the entire cfDNA. This complements traditional mutation-based liquid biopsy analyses for early cancer detection.
Multiomics: refers to the integrated approach of simultaneously analyzing multiple levels of biology or “omics” at once, including genomics, proteomics, epigenomics (modifications to the genome that primarily affect gene expression), transcriptomics (mRNA transcripts), metabolomics (components of metabolic processes), and more. This involves analyzing multiple biomarkers simultaneously, which provides a next level understanding of the disease and its progression.
AI and Machine Learning: Integrating AI and related algorithms can help in analyzing vast datasets generated by NGS, thereby improving the accuracy and speed of diagnosis.
As these innovations mature, the sensitivity of tools used in liquid biopsies improves, allowing for the detection of even lower concentrations of ctDNA, cfDNA or CTCs. The above techniques, particularly when combined, are leading to exponential improvements in both sensitivity and specificity, albeit at high compute and laboratory costs. Operating these specialized technologies and equipment for extracting, analyzing, and interpreting biomarkers from blood samples can incur costs in the thousands of dollars per test.
Commercialization
Numerous companies focused on blood-based MCED are in various stages of R&D, validation and clinical trials. As it stands, there is no path for MCED broad reimbursement or commercialization beyond cash payers and early adopters. This will require a legislative change to Title XVIII of the Social Security Act (establishing and governing Medicare) to provide Medicare coverage for MCED screening to drive broad based adoption. It is unclear if or when this might happen. False positives are prevalent and the relatively low precision of MCED can trigger diagnostic odysseys, placing an undue burden on both the patient and the healthcare system.
Single cancer indications, such as colorectal cancer screening (CRC), hold greater near-term promise as there are existing CMS and USPSTF reimbursement guidelines. The focused approach allows for greater reliability and accuracy. As soon as late stage clinical trials for CRC liquid biopsy screening clear FDA approvals, there is a direct path to reimbursement and commercial adoption. Companies poised to commercialize first are well positioned to initiate a liquid biopsy flywheel of scaled real-world data, propelling efficiencies of scale.
The Future
Liquid biopsies provide a non-invasive path for early detection and represent a significant leap forward in the medical diagnostic field, especially in early cancer detection and monitoring. While challenges like reimbursement and higher costs exist, continuous technological advancements and the potential for economies of scale promise a future where liquid biopsies become more accessible to a broader population. The focus remains on ensuring that as costs come down without affecting the reliability and accuracy of the tests. Companies harnessing platforms that emphasize a multifaceted approach while reducing infrastructure and laboratory costs are poised to have the largest impact in this exciting field.
