It was over a century ago that Thomas Ashworth first detected tumor-derived cells in the blood of a man with metastatic cancer, spurring an intense period of academic and clinical research looking into the role of such circulating tumour cells (“CTCs”) in the biology of metastasis, and the development of techniques with which to capture and study them. 1994 brought the discovery of DNA fragments, carrying genetic alterations mirroring those of the tumour, circulating freely in the bloodstream (“circulating tumour DNA”, or “ctDNA”).
A flurry of commercial activity has since followed, in pursuit of the development of liquid biopsy tests, which may be used to guide the selection of targeted treatments based on genomic profiles; the ‘holy grail’ of cancer management, and a highly lucrative opportunity for anyone that can find it. In, steps Pharma.
Janssen led the pack with its FDA-cleared (2004) CELLSEARCH® CTC Test, for the enumeration of CTCs in whole blood and outcomes prediction in metastatic breast cancer, signifying the first and only actionable test for the detection of CTCs in cancer patients. In 2016 Roche won approval for its cobas EGFR Mutation Test v2, the first blood-based companion diagnostic for identification of non-small cell lung cancer (NSCLC) patients eligible for treatment with Roche’s Tarceva®.
Today, there continues to be a growing interest from both Pharma and BioTech in a market projected to reach USD 6.8 bn by 2026 (just USD 1.2bn in 2020), with clear applications for innovative technologies in R&D, as well as in bolstering the use of in-line products. For example, leading precision oncology company GuardantHealth, a pioneer in the liquid biopsy space, offer GuardantOMNITM, a 500-gene panel designed for biopharma to accelerate development programs in immuno-oncology and targeted therapy, with partnerships in place with BMS, AstraZeneca and Merck. For use in the treatment of advanced cancers, Guardant’s Guardant360® became the first FDA-approved liquid biopsy test for comprehensive tumour mutation profiling across all solid tumours in 2020, and companion diagnostic to AstraZeneca’s Tagrisso® in 2020, and Amgen’s Lumakras® and J&J’s Rybrevant® in 2021. Roche-owned Foundation Medicine offer the most comprehensive FDA-approved liquid biopsy on the market with the FoundationOne® Liquid CDx, approved for the detection of specific biomarkers in NSCLC, prostate, ovarian and breast cancer, each of which is linked to an approved, targeted therapy. Similarly, biotechs offering promising technologies can cash-in via pharma services models, such as that agreed between Angle plc, who’s Parsortix CTC enrichment platform is under FDA review, with an unnamed Pharma company for USD 1bn in 2021.
Despite this progress, challenges remain in terms of clinical utility, around standardization across DNA extraction methods and analytic criteria, how often they should be used, hand ow useful they will be in the detection and management of early-stage cancers. Not to mention, who will burden the costs associated with such innovative technologies.
It is fair to say that there is a great deal potential, but a great deal of unknowns associated with these tests, and several hurdles to overcome before we see a complete move of liquid biopsy from bench to bedside.