Abstract 86P
Background
Nectin-4 is a transmembrane protein belonging to the family of cell adhesion molecules, essential for Ca2+-independent adherens junctions facilitating cell-cell interactions. These proteins play a crucial role in cellular viability and motility, particularly in cancer. Genetic alterations and aberrant expression of Nectin-4 have been observed in several malignancies. Enfortumab-vedotin, a Nectin-4-targeting antibody-drug conjugate (ADC), has demonstrated remarkable efficacy in urothelial carcinoma. However, its potential role in soft tissue sarcoma (STS) remains underexplored.
Methods
Amp defined by either CNV (Affymetrix single nucleotide polymorphism [SNP] 6.0 array data) or transcriptome (RNA-Seq_v2, log2- transformed RNA-Seq by expectation maximization [RSEM] normalized values) via cBioPortal. Query for amp of “NECTIN4” gene showed 287 samples of STS in 2 cohorts: Sarcoma TCGA, PanCancer Atlas – Cohort1 and ICGC TGCA Nature 2020- Cohort2.
Results
Cohort1 (253 patients) included undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), synovial sarcoma (SS), leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumor (MPNST). 12 % (31/253) exhibited amp of NECTIN4. The UPS group comprised 50 cases with 11 (22%) with amp. For MFS amp was observed in 5 out of 25 cases (20%). For 100 LMS cases, 5 (5%) had the amp. Among 59 DDLPS samples, 8 presented the amp (13%). Only 1 case in the SS group, out of 10 cases analyzed, exhibited amp. No amp was observed in the MPNST group (9 cases). Cohort 2 consisted of 2,922 samples across 38 cancers. The STS collection consisted of 34 cases, including 19 cases of DDLPS, with 16% (3/19) showing amp, and 15 cases of LMS, with an amp rate of 7%.
Conclusions
Our findings underscore the need for further investigation of Nectin-4 in STS, including immunohistochemical analysis and clinical trials with ADCs such as Enfortumab-vedotin, emphasizing the potential of cutting-edge therapies to improve outcomes in sarcomas.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
S. Orlando.
Funding
Has not received any funding.
Disclosure
B. Vincenzi: Financial Interests, Personal, Invited Speaker: Springworks, Deciphera, Boehringer Ingelheim, PharmaMar. All other authors have declared no conflicts of interest.