The importance of liquid biopsy MSI for studying tumors and immunotherapy applications

DATE: October 8, 2020

TIME:  10:00am PDT, 1:00pm EDT

Microsatellite instability (MSI) has evolved as a marker of potential hereditary cancer risk and is now a tissue agnostic immune biomarker with a broad reaching impact across cancer screening, tumor biology and cancer treatment outcomes. MSI-high is the first tissue agnostic predictive immune biomarker achieving FDA approval for immune checkpoint blockade therapy extended across multiple cancers irrespective of the anatomical tissue of origin and solely based upon a confirmed MSI-high status tumor biology. MSI is favorably predictive of anti-angiogenesis and radiation therapy benefit yet is an adversely detrimental predictive marker for cytotoxic chemotherapy. Intra- and inter-tumoral heterogeneity and dynamic cancer clonal evolution can be a limitation of tissue biopsies. Liquid biopsy MSI can overcome these dynamic clonal heterogeneity issues and will be able to extend MSI testing and potential durable immunotherapy survival benefits in the future to patients that otherwise have tissue acquisition limitations.

MSI guided cancer treatment is now extending to earlier stages of cancers based upon tumor biology and not anatomic stage. MSI may be sporadic or can result from germline MMR mutations defining the Lynch Syndrome. This hereditary identification has tremendous impact for both the individual with their cancer treatment decisions but can also guide more effective focused cancer screening of affected family members. MSI-high is a distinct tumor biology state with a differing cancer treatment benefit. Integrating liquid MSI as a potential dynamic response biomarker in cancer treatment clinical trials as well as tumor biology translational research studies with tumor mutational burden, co-mutations, angiogenesis, and other components of an immune hot versus cold tumor microenvironment are needed and is an important step forward to further extend the potential curability of cancer treatment.

Learning Objectives:

• Learn how MSI status can be detected in liquid biopsy samples. Review the cancer treatment outcomes in MSI tissue agnostic cancers.
• Outline the MSI tumor biology interaction with other immune biomarkers, oncogenic pathways, and mutations in cancer treatment.
• Discuss the future potential cancer research and clinical utility of liquid biopsy MSI.

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