Theranostic strategies in sarcoma: preliminary clinical evidence

Sarcomas encompass a highly diverse range of malignancies, characterized by varied morphological and molecular profiles. Treatment options in case of therapy-refractory or advanced disease are limited. In this context, theranostics emerges as an innovative platform seamlessly integrating diagnosis and therapy, offering promising prospects.

This special report delves into the initial clinical applications of theranostic-based approaches in sarcomas. Specifically, it examines various strategies targeting biomarkers associated with sarcomas, including fibroblast activation protein (FAP), prostate-specific membrane antigen (PSMA), C-X-C chemokine receptor type 4 (CXCR4) and somatostatin receptor 2 (SSTR2).

The heterogeneous uptake of the CXCR4-targeted radioligand in lesions, along with its poor correlation with immunohistochemistry data, diminishes the attractiveness of this theranostic approach in the sarcoma oncological setting. SSTR2-targeted approaches in sarcoma, although potentially effective, are limited to a single case. Early experiences with FAP inhibitors in sarcoma patients have shown particularly promising outcomes, indicating effective disease control with minimal toxicity. While PSMA presents an enticing target for theranostic approaches in sarcomas, its utilization remains anecdotal and requires further investigation. Prospective and well-designed clinical trials are imperative to delineate the potential impact of FAPI- and PSMA-based approaches on sarcoma therapeutic landscapes, offering innovative and personalized treatment options.