The Cutting Edge of Oncology: MRD for Solid Tumors

We know MRD detection is feasible and widely employed for hematological cancers… but what does the future hold for solid tumor MRD technologies? Written by Alex Kernagis, Rayna Saldanha, Claire Liddy and Bryan Kaplan.

A New Frontier

The niche space of minimal residual disease testing is quickly growing within the world of biotech due to great strides in sequencing and biopsy technology development over the last decade. Minimal residual disease (MRD) is a term used to describe detectable residual fragments of cancer in patients who have had cancer treatment with a curative intent such as surgery or chemotherapy. The presence of these cancer fragments post-treatment have been shown to put patients at a higher risk of cancer relapse.

Caveats for Solid Tumors

When compared to hematological cancers, solid tumors yield far lower amounts of detectable biomarkers post-resection — resulting in the need for far greater performance requirements to detect residual disease. In addition, most solid tumors are genetically unique to individual patients, making it harder to use standardized and non-personalized assays. These assays are more difficult to design and have more intensive sequencing requirements.

The Importance of Sequencing

The development of most MRD assays for solid tumors, especially for the creation of personalized assays for individual patients, utilize resected tumor tissue to identify patient-specific tumor mutation targets that are subsequently built into the assay. Most assays within the industry are in fact tumor-informed, allowing the technology to achieve the sensitivities and specificities required to ensure extremely low false positive rates and proper biomarker detection rates. The need for rigorous sequencing is arguably the largest differentiating factor between current hematological and upcoming solid-tumor assays.

Emerging Technologies

There are currently a handful of firms in the industry that are in the process of developing the assays required to detect MRD for solid tumors, each of which has a different style of biomarker detection and sequencing method.

Future Developments and Insights

There also exist outlier technologies that are beginning to challenge traditional whole exome sequencing with ultra-high coverage values. We are beginning to see companies experiment with the use of extremely low coverage values, allowing for greater breadth, input material and optimal detection sites. In addition, methylation techniques have arisen as one of the largest challengers to traditional sequencing, especially for early cancer detection, and also show promise for monitoring purposes. Another growingly successful technology has been the development of CTC (circulating tumor cell) capture technologies that can be used in combination with ctDNA biopsy platforms — effectively creating a safety net for detection and significantly boosting overall sensitivity.

Acquisitions of ArcherDx and GRAIL

Looking Forward

The industry is increasingly growing in size, and in a best-case scenario, the most successful commercially available assays for monitoring solid tumor MRD will hopefully begin to hit the market throughout the next couple years. Many large bets on the efficacy of the industry have been wagered in the form of multi-billion dollar acquisitions by biotechnology companies, the largest of which have been the acquisitions of ArcherDx and GRAIL by Invitae and Illumina, respectively.

The newest student-run healthcare and life-sciences consulting group at the Johns Hopkins University