Landscape of early cancer detection using blood tests

Imagine that you go for your annual doctor’s appointment, where they draw your blood to check your cholesterol, thyroid, liver enzymes and, also run a test for cancer, before you have any cancer symptoms. I am talking about a blood test to detect not just a few types of cancer but for all 100-plus of them- — including hard-to-find forms like pancreatic and ovarian. At this early stage, if you receive a diagnosis of cancer, it is more likely to be local and not advanced so that a cure is not only possible but likely.

 

Early multi-cancer tests would bring a radical shift in the way cancer is detected, just by using a single blood draw. This is to be done through analysing circulating tumour cell-free DNA and leveraging genomic technologies and machine learning. However, for effective large-scale population screening, a blood test should balance sensitivity and specificity, and be able to predict tissue of origin, while minimising potential test-associated risks, including over-diagnosis. 

Here is an overview of multi-cancer early detection blood tests in the pipeline:

 

Galleri test (detects 50+ cancers, often before symptoms present)

 

Company: GRAIL

Started in: 2015

How it works: The test works by detecting fragments of DNA in a blood sample via next-generation sequencing, which identifies DNA methylation, distinct patterns of which are associated with particular cancers, potentially allowing for the early detection of cancer and providing information of the origin of the cancer.       

Evidence: GRAIL’s first clinical trial for the Galleri test is the ‘Circulating Cell-free Genome Atlas Study’. In a paper published in March 2020, researchers show that a blood test could detect more than 50 different types of cancer, with a false positive rate of < 1%. The test was able to predict the tissue in which the cancer originated in 96% of samples and it was accurate in 93% of cases [1].

Availability: The Galleri test is not yet commercially available and is currently available only to participants of GRAIL’s clinical studies (STRIVE, SUMMIT, and PATHFINDER studies).

CancerSEEK (detects 16 cancers, before noticeable symptoms occur)

Company: Thrive
Started in: 2018

How it works: This test detects alterations in 16 genes associated with cancer, in pieces of tumor DNA circulating in the bloodstream. It also measures the blood levels of 9 proteins overproduced by some cancer types.

Evidence: DETECT-A (Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing) is the first ever prospective, interventional study to use a blood test to screen for multiple types of cancers in a real-world population. Out of 10,006 women who enrolled in the study, 26 eventually received a diagnosis of cancer first detected by the blood test. Thrive’s blood test detected cancers across ten different organs, including seven organs that do not have standard-of-care screening tools available. Notably, 65% of cancers detected by Thrive’s blood test were identified as local or regional disease, allowing for earlier intervention and if indicated, surgery with intent to cure. Maintaining a high specificity thereby minimizing “false-positive” results is essential for a multi-cancer blood test. Screening with Thrive’s blood test alone had a 98.9% specificity, and when combined with imaging had a specificity of 99.6% [2].

Availability: CancerSEEK is currently in development and is not yet available to patients. Information about enrolling in upcoming clinical trials will be provided on the company website.

PanSeer (5 cancers)- 477 differentially methylated regions

Company: Singlera Genomics

Started in: 2014

How it works: PanSeer assay measures distinct tumor-specific methylation patterns in adjacent methylation sites. The technology interrogates over 20,000 methylation marker patterns.

Evidence: PanSeer can detect cancer up to (stomach, esophageal, colorectal, lung and liver) four years before conventional diagnosis with 95% sensitivity and 96% specificity using circulating tumor methylated DNA [3].

Availability: For research use only.

ELSA-Seq test (12 cancers)

Company: Burning Rock Biotech
Started in: 2014

How it works: ELSA-seq is a sensitive targeted methylation sequencing assay that interrogates epigenetic alterations from circulating cell-free DNA (cfDNA), enabling simultaneous identification and localization of multiple cancer types. The target panel covers 80,672 CpG sites, spanning genomic regions of approximately 1.05 Mb. A total of 8312 co-methylation blocks served as markers to create the classification model.

Evidence: Results from THUNDER-II focused on malignancies developed in liver, colon/rectum, esophagus, pancreas, lung and ovary, of which four are gastrointestinal cancer types. Various stages were represented in the cancer group, and 79.5% patients were diagnosed at early stages (I-III). At 99.5% training specificity (95%CI: 96.7-100%), the cross-validated sensitivity was 79.9% (95%CI: 74.6-84.4%). The results were consistent in the validation set, with 98.3% specificity (95%CI: 95.8-99.4%) and 80.6% (76.0-84.6%) sensitivity across stages and cancer types. [4,5]

Availability: Check Burning Rock Biotech for service information.

About the Author

Jimita Toraskar, PhD in Medicine, works as a Scientist at PubGene AS. She plays a key role in identifying and evaluating evidence resulting in actionable insights for patients. Jimita participates in evaluation and specification of AI-assisted tools. Along with a strong background in pharmaceutical sciences, Jimita is a firm believer in the principles of user-centric design and constant learning.

References:

  1. Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV; CCGA Consortium. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA.Ann Oncol. 2020;31(6):745-759. doi:10.1016/j.annonc.2020.02.011
  2. Lennon AM, Buchanan AH, Kinde I, et al. Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention. Science. 2020;369(6499):eabb9601. doi:10.1126/science.abb9601
  3. Chen X, Gole J, Gore A, et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test.Nat Commun. 2020;11(1):3475. Published 2020 Jul 21. doi:10.1038/s41467-020-17316-z
  4. Gao Q, Li B, Cai S, et al. Early detection and localization of multiple cancers using a blood-based methylation assay (ELSA-seq). Presented at: 2020 ESMO Congress; November 20-22, 2020; Virtual. Abstract LBA3.
  5. Li B, Xu J, Wang C, et al. Multiplatform analysis of early-stage cancer signatures in blood. Presented at: AACR Special Conference on Advances in Liquid Biopsies; January 13-January 16, 2020. Abstract 62552825.