Updated cancer treatment framework offers new guidance on actionability and resistance biomarkers

by European Society for Medical Oncology

edited by Sadie Harley, reviewed by Andrew Zinin

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ESMO has published version 2 of the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT), a major update to the internationally recognized precision oncology framework that helps oncologists assess the clinical relevance of molecular alterations and match patients with the most appropriate targeted therapies.

First introduced in 2018, ESCAT provided a common language for ranking genomic alterations according to the strength of evidence supporting their use in precision oncology. Since then, the field has evolved, with broad adoption of tumor sequencing, the emergence of tumor-agnostic therapies, growing use of real-world evidence and increasing recognition of biomarkers that predict resistance to treatment.

These advances created the need for an updated framework that reflects contemporary clinical practice and supports confident decision-making.

Published in Annals of Oncology, ESCAT v2 retains the core principles that made the original scale widely adopted while introducing several refinements designed to increase clarity, consistency and ultimately patient benefit.

Among the most significant updates is the restructuring of Tier I, which now explicitly distinguishes between different levels of certainty supporting a biomarker-treatment match while maintaining the same clinical recommendation for use.

The new framework also incorporates formal criteria for evaluating tumor-agnostic therapies through alignment with ESMO's Tumor-Agnostic Classifier and Screener (ETAC-S), provides more granular guidance on the use of prospective and real-world evidence and refines the lower tiers to better reflect current evidence generation pathways.

ESCAT v2 introduces what is believed to be the first systematic, evidence-based resistance scale developed independently of regulatory approvals. The new parallel framework enables clinicians to classify biomarkers associated with reduced or absent treatment benefit, supporting more informed therapeutic sequencing and treatment selection.

"Precision oncology has matured considerably since the original ESCAT was published," said Dr. Aya El Helali, first author of the Annals of Oncology paper.

"Clinicians today are faced with a far greater volume and diversity of biomarker information than ever before. ESCAT v2 provides a more nuanced and practical framework for interpreting both actionability and resistance biomarkers, helping translate increasingly complex molecular data into treatment decisions that benefit patients," she explained.

The updated framework is intended for integration into molecular diagnostic reports, molecular tumor board discussions, clinical practice guidelines and everyday treatment planning.

By providing a transparent, evidence-based assessment of biomarker relevance, ESCAT v2 supports oncologists in navigating the growing complexity of cancer care while fostering more consistent application of precision medicine across health care systems.

"One of ESMO's core responsibilities is to help oncology professionals keep pace with rapidly evolving science and translate evidence into better patient care," said ESMO President Fabrice André, who was in the group that developed the first version of ESCAT.

"ESCAT v2 exemplifies ESMO's commitment to developing practical frameworks and guidance that support clinicians in making informed decisions in an increasingly data-rich and complex oncology landscape," he continued.

As outlined in the ESMO Roadmap 2030, supporting the effective implementation of precision oncology remains a strategic priority for the society. ESCAT v2 represents another step toward ensuring that every patient undergoing molecular testing receives a clear, evidence-based interpretation of findings that can guide treatment decisions.

Publication details

A. El Helali et al., The ESMO Scale for Clinical Actionability of Molecular Targets, version 2 (ESCAT v2): an evidence-based framework for ranking alterations as actionability and resistance biomarkers in precision oncology, Annals of Oncology (2026). DOI: 10.1016/j.annonc.2026.09.008

Journal information: Annals of Oncology

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OncologyClinical genetics Provided by European Society for Medical Oncology Who's behind this story?

Sadie Harley

BSc Life Sciences & Ecology. Microbiology lab background with pharmaceutical news experience in oil, gas, and renewable industries. Full profile →

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