Patterns of care and outcome of <i>CIC</i>‐rearranged sarcoma patients: A nationwide study of the French sarcoma group

Brahmi, Mehdi; Gaspar, Nathalie; Gantzer, Justine; Toulmonde, Maud; Boudou‐Rouquette, Pascaline; Bompas, Emmanuelle; Firmin, Nelly; Valentin, Thibaud; Cancel, Mathilde; Duffaud, Florence; Bertucci, François; Perrin, Christophe; Dufresne, Armelle; Marec‐Bérard, Perrine; Jean-Denis, Myriam; Loarer, François Le; Pierron, Gaille; Tirode, Franck; Blay, Jean‐Yves; Watson, Sarah

doi:10.1002/cam4.5539

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Depending on tumor tissue availability, RT‐PCR, next‐generation RNA sequencing (RNA seq) or clustering, and methylation profile were performed on paraffin‐embedded and/or fresh frozen tissue 2,4,20 . Recently, all cases of tumors with pathological Ewing characteristics that do not harbor the canonic EWS fusion transcript, were systematically analyzed with RNA sequencing and/or RT‐PCR with specific combination of primer sets for CIC::DUX4 and BCOR and/or FISH analysis with probes for CIC (19q13.2) , for BCOR a dual color break apart probe (Xp 11.4) and for YWHEA (17p13.3) 11,21,22 . The order of this techniques varies according to each institutional organization.…”

Section: Methodsmentioning

confidence: 99%

“… 2 , 4 , 20 Recently, all cases of tumors with pathological Ewing characteristics that do not harbor the canonic EWS fusion transcript, were systematically analyzed with RNA sequencing and/or RT‐PCR with specific combination of primer sets for CIC::DUX4 and BCOR and/or FISH analysis with probes for CIC (19q13.2) , for BCOR a dual color break apart probe (Xp 11.4) and for YWHEA (17p13.3). 11 , 21 , 22 The order of this techniques varies according to each institutional organization. For some old cases, analysis could have been performed retrospectively.…”

Section: Methodsmentioning

confidence: 99%

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Clinical characteristics and outcomes for children, adolescents and young adults with “CIC‐fused” or “BCOR‐rearranged” soft tissue sarcomas: A multi‐institutional European retrospective analysis

et al. 2023

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinical characteristics and outcomes for children, adolescents and young adults with “CIC‐fused” or “BCOR‐rearranged” soft tissue sarcomas: A multi‐institutional European retrospective analysis

et al. 2023

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“…Frontiers in Cell and Developmental Biology frontiersin.org along with clinical outcomes data of patients with CIC-rearranged tumors who undergo multimodal treatment strategies (surgery, radiation, and chemotherapy) have been extensively discussed elsewhere (Antonescu et al, 2017;Connolly et al, 2022;Brahmi et al, 2023;Murphy et al, 2024). Therefore, in this review we will only briefly mention the standard chemotherapy backbones and largely focus on the emerging mechanism-based approaches to target CIC-fused sarcomas.…”

Section: Current and Emerging Strategies To Treat Advanced Human Cicr...mentioning

confidence: 99%

Molecular and therapeutic advancements in Capicua (CIC)-rearranged sarcoma

Ponce,

Luck,

Okimoto

2024

Front. Cell Dev. Biol.

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Capicua (CIC)-rearranged sarcomas are an aggressive subset of undifferentiated round cell sarcomas. CIC::DUX4, the proto-typical CIC fusion oncoprotein is associated with rapid clinical progression and chemotherapy resistance leading to poor clinical outcomes. Recent studies have identified additional CIC fusions (CIC::NUTM1, CIC::FOXO4, and CIC::LEUTX) that largely retain CIC-binding specificity but leverage C-terminal binding partners (NUTM1, FOXO4, and LEUTX) to potentially activate transcriptional programs that drive oncogenesis. Moreover, the recent development of preclinical models to study CIC::DUX4 sarcoma have advanced our understanding of the underlying biological mechanisms and uncovered key dependencies that can be translated into rational therapies. In this review, we will highlight these recent advancements in CIC-rearranged sarcoma biology with a vision for clinical translation to improve patient outcomes.

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“…SARC0095, a CIC-rearranged Ewing-like sarcoma, exhibited significant sensitivity to gemcitabine and docetaxel (viability score: 36). Gemcitabine-based regimens have been reported as inducing two partial responses in a recent study investigating clinical management and outcomes for CIC-rearranged sarcomas 42 . The combination of vinorelbine and mocetinostat is currently in trials for rhabdomyosarcoma 43 .…”

Section: Sample Typementioning

confidence: 99%

The landscape of drug sensitivity and resistance in sarcoma

Al Shihabi,

Tebon,

Nguyen

et al. 2023

Preprint

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Sarcomas are a family of rare malignancies composed of over 100 distinct histological subtypes. The rarity of sarcoma poses significant challenges in conducting clinical trials to identify effective therapies, to the point that many rarer subtypes of sarcoma do not have standard-of-care treatment. Even for established regimens, there can be substantial heterogeneity in responses. Overall, novel, personalized approaches for identifying effective treatments are needed to improve patient outcomes. Patient-derived tumor organoids (PDTOs) are clinically relevant models representative of the physiological behavior of tumors across an array of malignancies. Here, we use PDTOs as a tool to better understand the biology of individual tumors and characterize the landscape of drug resistance and sensitivity in sarcoma. We collected n=194 specimens from n=126 sarcoma patients, spanning 24 distinct subtypes. We characterized PDTOs established from over 120 biopsy, resection, and metastasectomy samples. We leveraged our organoid high-throughput drug screening pipeline to test the efficacy of chemotherapeutics, targeted agents, and combination therapies, with results available within a week from surgery. Sarcoma PDTOs showed patient-specific growth characteristics and subtype-specific histopathology. Organoid sensitivity correlated with diagnostic subtype, patient age at diagnosis, lesion type, prior treatment history, and disease trajectory for a subset of the compounds screened. We found 90 biological pathways that were implicated in response to treatment of bone and soft tissue sarcoma organoids. By comparing functional responses of organoids and genetic features of the tumors, we show how screenings can provide an orthogonal set of information to facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes in sarcoma. In aggregate, we could identify at least one effective FDA-approved or NCCN-recommended regimen for 59% of the specimens tested, providing an estimate of the proportion of immediately actionable information identified through our pipeline.

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Patterns of care and outcome of CIC‐rearranged sarcoma patients: A nationwide study of the French sarcoma group

Cited by 8 publications

References 23 publications

Clinical characteristics and outcomes for children, adolescents and young adults with “CIC‐fused” or “BCOR‐rearranged” soft tissue sarcomas: A multi‐institutional European retrospective analysis

Clinical characteristics and outcomes for children, adolescents and young adults with “CIC‐fused” or “BCOR‐rearranged” soft tissue sarcomas: A multi‐institutional European retrospective analysis

Molecular and therapeutic advancements in Capicua (CIC)-rearranged sarcoma

The landscape of drug sensitivity and resistance in sarcoma

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