The evolving paradigm of biomarker actionability: Histology-agnosticism as a spectrum, rather than a binary quality

Precision medicine is progressively revolutionizing oncology, through the identification of biomarkers predictive of treatment response in cancer patients. For three of such biomarkers, namely NTRK-fusions, microsatellite instability and high tumor mutational burden, drugs have been approved by regulatory agencies regardless of tumor histology, realizing the paradigm of histology-agnostic actionability. Several additional biomarkers are being studied in a histology-agnostic manner, and may in the future expand this list. However, most available evidence suggest that histology-agnosticism may be the extreme of a continuous spectrum of actionability, rather than a binary quality. The present review recapitulates such evidence, highlighting opportunities and challenges posed by the emergence of the spectrum of biomarker actionability in the context of a prevalently histology-based oncology.