How will liquid biopsy change cancer care?
LIQUID BIOPSY: A POWERFUL EMERGING TOOL FOR CANCER CARE, AND A HUGE BUSINESS OPPORTUNITY
Cancer is a rising concern in modern society. Numerous drivers contribute to the increase of cancer cases, such as ageing of the population, lifestyle, and environment. According to the World Health Organization, cancer is responsible for one in six deaths worldwide, and one in two people are likely to develop cancer in their lifetime. Cancer cells are cells whose genes have mutated; in order to understand each cancer’s mechanisms and determine the appropriate treatment, these tumors require analysis. Traditional biopsy methods involve obtaining a piece of the tumor through invasive surgery. However, these procedures are expensive and exhausting for the patient, and cannot be reproduced regularly in order to monitor a cancer’s evolution and treatment efficiency over time. However, it is now possible to avoid such invasive procedures thanks to a “liquid biopsy”. Indeed, it is possible to collect a simple blood draw in which relevant biomarkers can provide useful information about the patient’s cancer. In particular, a number of companies are developing technologies to collect, isolate, and analyze circulating tumor DNA (ctDNA: DNA molecules shed by cancerous cells) and circulating tumor cells (CTCs: tumor cells shed from the original tumor) that spread into the bloodstream. Thanks to these tools, it is possible to not only diagnose cancer uninvasively, but also to understand the molecular mechanisms associated with each patient, choose and develop a tailored treatment, monitor the treatment’s efficiency (along with drug resistance), and screen for disease recurrence. Some companies are even working on screening for early detection, although this is a more long-term application.
Liquid biopsy thus has the potential to assist at every stage of cancer care, saving lives and cutting healthcare costs. The opportunity is huge, and the associated market is already large and growing extremely fast. According to this Yole Développement report, the liquid biopsy market will grow from $1.7B in 2017 at a CAGR2017-2023 of 29%, reaching $7.8B by 2023. This includes hardware (systems and devices) and reagent kit sales, along with service revenue, for CTC and ctDNA applications.
AN IMPRESSIVE RANGE OF COMPANIES AND BUSINESS MODELS
Studying mutations in cancer cells’ DNA is not an easy task, and requires many different tools and skills. From the enrichment and analysis of biomarkers to the bioinformatics analysis of mutation profiles, the path is long and many players are involved. This report confirms the role of each player at each level of the supply chain, explains who is specialized in which step, and details where the value lies and how the development of liquid biopsy is boosting downstream analysis equipment markets like sequencing and digital PCR. The difference and complementarity of ctDNA and CTCs is also described, and Yole Développement’s analysts explain why CTC has yet to attract significant funding, and how the situation may now change thanks to recent findings.
Indeed, ctDNA companies have raised more than $3.7B since 2010, while CTC companies have only raised around $280M. In terms of revenue, the split is also unbalanced in favor of ctDNA companies. This is primarily due to business models: most ctDNA companies offer testing services in their Clinical Laboratory Improvement Amendments (CLIA) labs, performing tests developed in-house which do not require Food and Drug Administration (FDA) clearance. Moreover, DNA is easier to transport and store than live cells, which is another advantage for ctDNA. On the contrary, most CTC companies are developing instruments that are directly sold to endusers, along with the associated consumables.
However, most of these instruments for CTC isolation are still for research use only because the FDA requires more evidence of the benefits derived from analyzing CTCs in patients’ survival rate, before approving them for clinical use. This explains, at least partially, why CTC companies are lagging behind in terms of revenue. Thankfully, this situation may soon change thanks to advances in technology and to the increasing number of published works proving the clinical value of CTC analysis: in fact, a complete live cell can carry much more information than a DNA strand.
TECHNOLOGICAL BREAKTHROUGHS ARE DRIVEN BY MICROFLUIDIC TECHNOLOGY
Many steps in the liquid biopsy workflow have been made possible thanks to microfluidic technologies. From isolation to downstream analysis, microfluidic devices are involved everywhere. A major part of CTC enrichment and isolation systems relies on microfluidic devices that enable separation of CTCs from other blood cells, using their physical properties such as size, shape, deformability, and dielectric properties. Important companies such as Angle plc, Celsee, Clearbridge Biomedics, and Vortex Biosciences rely on microfluidics. These microfluidic methods work for a wide range of cells and enable high throughput capture at a low cost. Moreover, downstream analysis solutions also rely on microfluidic technologies in numerous cases: DNA sequencers from Illumina, Ion Torrent, and others use microfluidic flow cells, and other technologies like droplet digital PCR from Bio- Rad, Stilla Technologies, and RainDance (acquired by Bio-Rad) are also microfluidic technologies.
All of these state-of-the-art technologies are enabled by innovative microfluidic hardware and allow more complex analyses to be performed, thus contributing to concrete improvements in cancer care. In this report, Yole Développement focuses on these microfluidic technologies at every level of the liquid biopsy workflow.
OBJECTIVES OF THE REPORT
- Explain what liquid biopsy is, why it is used, and the characteristics of each biomarker (ctDNA,CTC, exosomes)
- Show what constitutes “state-of-the-art” is today and what is expected for tomorrow, and understand the positive and negative impacts on the adoption of liquid biopsy for clinical use
- Provide a players overview at each supply chain level, from enrichment and isolation to downstream analysis, for CTC and ctDNA applications
- Provide a list and analysis of fundraisings and M&A
- Provide an analysis of the business models used in the liquid biopsy fiel