Introducing fluorescence guided surgery into orthopedic oncology: A systematic review of candidate protein targets for Ewing sarcoma

Abstract

Ewing sarcoma (ES), an aggressive bone and soft‐tissue tumor, is treated with chemotherapy, radiotherapy, and surgery. Intra‐operative distinction between healthy and tumorous tissue is of paramount importance but challenging, especially after chemotherapy and at complex anatomical locations. Near infrared (NIR) fluorescence‐guided surgery (FGS) is able to facilitate the determination of tumor boundaries intra‐operatively, improving complete resection and therefore survival. This review evaluates potential ES‐specific proteins from the literature as targets for NIR FGS.

Role of immunotherapy in Ewing sarcoma

“…This form of imaging uses overexpressed tumor-associated membrane proteins to visualize tumors. 194 The near infrared fluorescence imaging has been explored for targeted imaging, and it provides an optical contrast Open access between tumor and its surrounding healthy tissue in preclinical tumor types and is an attractive approach to better delineate soft tissue involvement of ES during surgery. For ES surface membranes, proteins such as LINGO1, CD99, NOTCH1, CXCR4, c-Kit and NYPRY1 (table 2) have been proposed as potential targets.…”

“…For ES surface membranes, proteins such as LINGO1, CD99, NOTCH1, CXCR4, c-Kit and NYPRY1 (table 2) have been proposed as potential targets. 194 ADOPTIVE CELLULAR IMMUNOTHERAPIES: CAR T CELLS T cells engineered to express CARs can be used to effectively target tumor cells. CARs combine a binding domain against a surface antigen with signaling domains inducing T cell activation.…”

“…In addition to their use as immunotherapeutic targets surface antigens can potentially be used as diagnostic markers. 194 Accordingly, targeted imaging has been used to aid with ensuring tumor-free surgical margins. This form of imaging uses overexpressed tumor-associated membrane proteins to visualize tumors.…”

“…For ES surface membranes, proteins such as LINGO1, CD99, NOTCH1, CXCR4, c-Kit and NYPRY1 ( table 2 ) have been proposed as potential targets. 194 …”

Candidate Biomarkers for Specific Intraoperative Near-Infrared Imaging of Soft Tissue Sarcomas: A Systematic Review

“…In order to select the optimal biomarkers for tumor specific NIRF imaging in STS, we developed a target selection scoring system. The scoring system is based on the modified version of the Target Selection Criteria (TASC), developed by Bosma et al [ 24 ]. The scoring system is based on five domains (see Table 1 ).…”