image: Figure 1: Overview of MI Cancer Seek workflow. MI Cancer Seek begins with total nucleic acid (TNA) extraction from formalin-fixed, paraffin-embedded (FFPE) tissue slides. A minimum 20% tumor content and 25 mm2 is required, which is obtained through manual microdissection if required. During library preparation, RNA is labeled during first strand cDNA synthesis. Sequencing is performed on qualified Illumina NovaSeq 6000 instruments. Raw data is processed by Caris’ proprietary bioinformatics pipeline, and a report is generated that includes CDx biomarkers (level 1 evidence), clinically relevant biomarkers (level 2 evidence), and biomarkers with possible clinical significance (level 3 evidence). Abbreviations: CNV: copy number variation; EBV: Epstein-Barr virus; GPS: genomic probability score; HLA: human leukocyte antigen; HPV: human papilloma virus; HRD: homologous recombination deficiency; INDEL: insertion/deletion; LoH: loss of heterozygosity; MCPyV: Merkel cell polyomavirus; MSI: microsatellite instability; SNV: single nucleotide variant; TMB: tumor mutational burden. Created in BioRender. Ribeiro, J. (2025) https://BioRender.com/m29z318.
Credit: Copyright: © 2025 Domenyuk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
“Accordingly, MI Cancer Seek represents a safe and effective comprehensive molecular test option supporting biomarker-directed care for oncology patients.”
BUFFALO, NY - August 15, 2025 – A new research paper was published in Volume 16 of Oncotarget on August 13, 2025, titled “Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay.”
In this study, first authors Valeriy Domenyuk and Kasey Benson, along with corresponding author David Spetzler from Caris Life Sciences in Irving, Texas, introduce MI Cancer Seek, an FDA-approved test designed to deliver comprehensive tumor profiling. MI Cancer Seek demonstrated strong concordance with other FDA-approved companion diagnostics and serves as a powerful tool to guide treatment decisions in both adult and pediatric cancer patients.
Cancer remains one of the most complex and diverse diseases to treat. With many targeted therapies currently FDA-approved, selecting the right one for a specific patient requires detailed genetic insights. MI Cancer Seek addresses this need by analyzing both DNA and RNA from a single tumor sample. The tool identifies key biomarkers linked to FDA-approved treatments for several major cancers, including breast, lung, colon, melanoma, and endometrial cancers.
One of the most significant strengths of MI Cancer Seek is its ability to deliver accurate and reliable results from minimal tissue input (50 ng). Even when analyzing formalin-fixed paraffin-embedded samples, which are widely used but often degraded, the test maintained high levels of accuracy. It successfully detected important genetic alterations such as PIK3CA, EGFR, BRAF, and KRAS/NRAS mutations and measured tumor mutational burden (TMB) and microsatellite instability (MSI), both of which are key indicators for immunotherapy response.
In clinical comparisons, the test achieved over 97% agreement with other FDA-approved diagnostic tools, confirming its reliability in detecting critical biomarkers. Notably, it showed near-perfect accuracy in identifying MSI status in colorectal and endometrial cancers. The researchers also demonstrated that the test maintains precision across different lab conditions and varying DNA input levels, confirming its robustness for routine clinical use.
Beyond its role as a companion diagnostic, MI Cancer Seek incorporates additional features developed under its predecessor, MI Tumor Seek Hybrid. These include detection of homologous recombination deficiency, structural variants, and cancer-related viruses. It also includes advanced tools such as the Genomic Probability Score for identifying the tissue of origin in cancers of unknown primary, as well as a gene signature to guide first-line chemotherapy in colorectal cancer.
“One limitation to be considered is the low PPA for ERBB2 CNA detection.”
By offering deeper genetic insights from a single, small sample, MI Cancer Seek has the potential to streamline diagnostics, reduce testing costs, and connect patients to effective therapies more quickly. As precision medicine continues to expand, this assay stands out as a comprehensive and efficient solution for meeting the evolving needs of modern oncology.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28761
Correspondence to: David Spetzler - dspetzler@carisls.com
Keywords: cancer, companion diagnostic, molecular profiling, solid tumors, precision oncology, next-generation sequencing
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About Oncotarget:
Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Not applicable
Article Title
Clinical and analytical validation of MI Cancer Seek®, a companion diagnostic whole exome and whole transcriptome sequencing-based comprehensive molecular profiling assay
Article Publication Date
13-Aug-2025
COI Statement
All authors have a financial relationship as employees of Caris Life Sciences.