Multi-Layered Molecular Profiling Informs the Diagnosis and Targeted Therapy of Desmoplastic Small Round Cell Tumor
Multi-omics profiling can inform treatment decisions in desmoplastic small round cell tumor, with a 62% disease control rate observed in patients receiving recommended therapies.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This study analyzed molecular profiles in 30 refractory desmoplastic small round cell tumor (DSRCT) patients to inform treatment options. Molecular-based management recommendations were made for 28 patients (93%), with 13 receiving recommended therapies. Disease control was achieved in 8 patients (62%) with partial or stable responses.
Abstract
<title>Abstract</title> <p> Desmoplastic small round cell tumor (DSRCT) is an ultra-rare sarcoma with limited treatment options. We performed whole-genome/exome, transcriptome, and DNA methylome analysis in 30 refractory DSRCT patients, complemented by (phospho)proteomic profiling in nine, within a nationwide precision oncology program. In eight patients (27%), DSRCT was diagnosed based on molecular profiling. Although all patients had “quiet” genomes, 28 (93%) received 107 molecular-based management recommendations, including assessment of clinical trial eligibility in 17 (57%). Nearly half of recommendations (45%) were based on overexpression of tyrosine kinases, as well as SSTR3/5 and CLDN6, detected in 33% and 20% of cases, respectively. Thirteen patients (46%) received recommended therapies, yielding disease control in eight (62%; partial response, <italic>n</italic> = 5; stable disease, <italic>n</italic> = 3), including three long-lasting responses (≥ 12 months) to pazopanib and trastuzumab deruxtecan, triggered by ERBB2 overexpression in the absence of constitutive ERBB2 signaling. Thus, multi-omics profiling enables individualized DSRCT treatment. </p>