Harnessing tumor-agnostic biomarkers for precision medicine in lymphoma.

Tumor-agnostic therapies focus on shared molecular biomarkers independent of tissue of origin, allowing a single drug to target a common biomarker across different tumor types. Such targets with regulatory drug approvals include NTRK fusion, RET fusion, BRAF V600E mutation, FGFR1 rearrangement, HER2 overexpression, microsatellite instability or mismatch repair deficiency (MSI-H/dMMR), and high tumor mutational burden (TMB-H). Novel strategies against molecular alterations such as NRG1 fusion, ALK fusion, MTAP loss, KRAS G12C, TP53 Y220C and homologous repair deficiency (HRD) have also emerged. While the list of potential tumor-agnostic biomarkers continues to expand, contemporary efforts are still predominantly focused on solid cancers over hematological malignancies, including lymphoma, representing a peculiar and perhaps unwarranted strategic gap. In this review, we thus provide a narrative overview of currently approved tumor-agnostic therapies and highlight emerging biomarkers, addressing the need to focus on their potential application beyond solid tumors.