Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

Area of Science:

• Oncology
• Genetics
• Immunology

Background:

• The US FDA approved a novel cancer treatment based on microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) biomarkers in May 2017.
• This approval represents a significant shift towards biomarker-driven cancer therapy, moving beyond traditional tumor location-based treatments.
• Keytruda, previously approved for various cancers with PD-1/PD-L1 biomarkers, saw its indications expand with this new approach.

Purpose of the Study:

• To highlight the significance of the FDA's approval of a biomarker-based cancer treatment.
• To discuss the expansion of Keytruda's indications.
• To emphasize the role of pathologists in biomarker evaluation and linking molecular subtypes to histological features for targeted therapy.

Main Methods:

• Review of FDA approval data for MSI-H/dMMR cancer treatments.
• Analysis of Keytruda's expanded indications and associated biomarkers (PD-1/PD-L1).
• Discussion of the role of pathologists in interpreting molecular and histological data for patient selection.

Main Results:

• First tumor treatment approved based on a common biomarker (MSI-H/dMMR) rather than tumor site.
• Significant expansion of Keytruda's therapeutic applications.
• Identification of MSI-H/dMMR status in various malignancies, including colorectal and gastric carcinomas, linked to increased neoantigen load and immune response.

Conclusions:

• Biomarker-based patient selection, particularly MSI-H/dMMR, is crucial for modern targeted cancer therapy.
• Pathologists are essential in bridging molecular classification and histological features, enabling effective targeted treatment strategies.
• The development signifies a paradigm shift in oncology, prioritizing genetic profiles for treatment decisions.