Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jul:7:e2300065.
doi: 10.1200/PO.23.00065.

Activity of Type II RAF Inhibitor Tovorafenib in a Pediatric Patient With a Recurrent Spindle Cell Sarcoma Harboring a Novel SNX8-BRAF Gene Fusion

Katharine Offer  1 , Michael T McGuire  2 , Kunchang Song  3 , Michael J Goldfischer  3 , Monika A Davare  4 , Christopher L Corless  5 , Carol Beadling  6 , Tanaya Neff  5 , Michael C Cox  7 , Sandya Govinda Raju  7 , Samuel C Blackman  7
Affiliations

Activity of Type II RAF Inhibitor Tovorafenib in a Pediatric Patient With a Recurrent Spindle Cell Sarcoma Harboring a Novel SNX8-BRAF Gene Fusion

Katharine Offer et al. JCO Precis Oncol. 2023 Jul.
No abstract available

PubMed Disclaimer

Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
(A) Treatment summary; data cutoff November 16, 2022. (B) Structure of the SNX8-BRAF fusion protein. The structure of the canonical BRAF protein sequence (UniProtKB—P15056 [BRAF_HUMAN]: UniProt) and the predicted SNX8-BRAF fusion protein, including functional domains, are shown. The SNX8 and BRAF exons, from which the protein sequences are derived, are represented by the numbers below the bars. This rearrangement is predicted to replace the N-terminal regulatory domain of BRAF with almost the entire SNX8 sequence, while leaving the BRAF kinase domain intact. (C) H&E × 10: spindle tumor cells with geographic necrosis (right upper corner); (D) HE × 20: pleomorphic tumor cells with frequent mitoses (in the center). CR, complete response; FISH, fluorescence in situ hybridization; H&E, hematoxylin and eosin; PD, progressive disease.
FIG 2.
FIG 2.
Activity of tovorafenib. Magnetic resonance images of mediastinal mass extending circumferentially around the aorta and impressing on the left atrium and pulmonary veins are indicated by white arrows in AP and lateral views. After two cycles of treatment with tovorafenib, only a trace of nonenhancing soft tissue surrounds the descending thoracic aorta. AP, anteroposterior.
See this image and copyright information in PMC

References

    1. Davis JL, Al-Ibraheemi A, Rudzinski ER, et al. Mesenchymal neoplasms with NTRK and other kinase gene alterations. Histopathology. 2022;80:4–18. - PubMed
    1. Laetsch TW, Roy A, Xu L, et al. Undifferentiated sarcomas in children harbor clinically relevant oncogenic fusions and gene copy-number alterations: A report from the Children's Oncology Group. Clin Cancer Res. 2018;24:3888–3897. - PMC - PubMed
    1. Hong DS, DuBois SG, Kummar S, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: A pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21:531–540. - PMC - PubMed
    1. Marcus L, Donoghue M, Aungst S, et al. FDA approval summary: Entrectinib for the treatment of NTRK gene fusion solid tumors. Clin Cancer Res. 2021;27:928–932. - PubMed
    1. Kao YC, Fletcher CDM, Alaggio R, et al. Recurrent BRAF gene fusions in a subset of pediatric spindle cell sarcomas: Expanding the genetic spectrum of tumors with overlapping features with infantile fibrosarcoma. Am J Surg Pathol. 2018;42:28–38. - PMC - PubMed

Publication types