Gastrointestinal Stromal Tumor

Patients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered.

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts. Previously presented at the 2024 ESMO Sarcoma and Rare Cancers Congress.

ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.

P=N/A, N=61, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

P=N/A, N=70, Not yet recruiting, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi

P=N/A, N=107, Not yet recruiting, Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University; The First Affiliated Hospital of Nanjing Medical Universit

Finally, four prominent subtypes are proposed with different genomic features, expression profiles, immune characteristics, clinical characteristics and subtype-specific treatment strategies. This large-scale analysis depicts the landscape and provides further insights into GIST pathogenesis and precise treatment.

Selecting appropriate immunohistochemical stains based on H&E morphology is the key to avoiding diagnostic pitfalls. Medical history and molecular genomic information greatly assist in correctly diagnosing NENs and their mimics.

C-KIT has been studied as the first biomarker for targeted therapy. Herein we review its structure, function and role in various non-neoplastic and neoplastic diseases.

It is also important to consider morphologic and immunophenotypic changes associated with treatment, including the potential absence of kit expression, particularly in GISTs that have metastasized. Therefore, obtaining clinical information regarding prior therapy with a tyrosine kinase inhibitor (TKI) is crucial.

Primary gastric epithelioid angiosarcoma is a rare gastric tumor. Given the epithelioid cell features displayed by tumor cells and the high expression of epithelial markers in tumor cells (83%), preoperative diagnosis is difficult and should be differentiated from adenocarcinoma or gastrointestinal stromal tumor.

The MIF/CXCR4 axis is the most common ligand-receptor interaction between macrophages and tumor cells. GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis.

International collaborations have been deployed in order to increase the clinical and biological knowledge of this orphan pathology in pediatrics.

This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.

In 3 cases, this increase reflected the occurrence or worsening of imatinib side effects. This case-series highlights the clinical impact of SARS-CoV-2 infection on the management of patients with GIST treated with imatinib.

P1/2, N=120, Recruiting, Deciphera Pharmaceuticals, LLC | Not yet recruiting --> Recruiting

Despite the significant improvement in treatment outcomes with adjuvant imatinib therapy for patients, drug resistance remains a major challenge for GIST therapy...The OXPHOS pathway is a promising therapeutic target in combination with TKI against sensitive KIT/PDGFRA mutants. Comprehensive understanding of the above resistance mechanisms, experimental drugs/strategies and metabolic changes is critical to implement the proper therapy strategy and improve the clinical therapy outcomes for GIST.

This case underscores the necessity of total gastrectomy with lymph node dissection due to the high incidence of metastasis in GISTs associated with Carney's triad. Further research is required to determine the optimal extent of lymph node dissection in such cases.

P1, N=157, Not yet recruiting, Kura Oncology, Inc.

P3, N=40, Not yet recruiting, Ascentage Pharma Group Inc.

P=N/A, N=600, Active, not recruiting, Peking University | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Mar 2025 | Trial primary completion date: Feb 2024 --> Nov 2024

55% (42/77) of liquid samples with a KIT -driver mutation had a co-occurring imatinib-resistant alteration, and a minority of cases harbored non- KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations... Known driver and TKI-resistant mutations are identified in liquid biopsies of patients with GIST, with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification of GIST during the medical management of advanced disease.

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was favorable for pts with KIT exon 11 + 17/18 mutations in the ripretinib arm.

Furthermore, a chronological analysis was performed using multiple resected archived samples from the same case, and revealed that diffuse IGF-II expression may have occurred in the early phase of tumor development. The present study catalogued the characteristics of GIST with hypoglycemia with a focus on NICTH-GIST.

P1/2, N=120, Not yet recruiting, Deciphera Pharmaceuticals, LLC

P=N/A, N=168, Completed, First Affiliated Hospital, Sun Yat-Sen University

P=N/A; Trial primary completion date: Dec 2025 --> Dec 2024

The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first-line treatment for metastatic GIST...B7-H3 is expressed at a particularly high rate in GISTs. This suggests that B7-H3 might operate as part of an immune checkpoint in GISTs.

Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

P=N/A, N=100, Recruiting, iOMEDICO AG

In addition, we showed that recovering EPHA2 expression via plasmid-induced overexpression of EPHA2 or schisandrin C, a natural product, could prevent regorafenib-induced cardiotoxicity. These findings demonstrated that regorafenib causes cardiomyocyte apoptosis and cardiac injury by reducing the expression of EPHA2 and schisandrin C could prevent regorafenib-induced cardiotoxicity by recovering EPHA2 expression, which provides a potential management strategy for regorafenib-induced cardiotoxicity and will benefit the safe application of regorafenib in clinic.

He was treated with surgical resection with negative margins and imatinib therapy. Postoperative surveillance showed no evidence of malignancy and the patient experienced a positive response to treatment with stable hemoglobin levels and significant weight gain.

To illustrate these points, we conclude with a case from our clinic involving a 15-year-old female with multiple CD117-positive gastric GISTs and a quadruple-negative wild-type genetic profile who required urgent surgical intervention following a failed tumor embolization. This case underscores the critical need for early diagnosis and individualized therapeutic strategies combining oncologic and surgical care to improve outcomes in pediatric GIST patients.

This study analyzed the heterogeneity and stem cell properties of ICCs in GISTs, revealing the molecular mechanisms and potential therapeutic targets for GISTs.

Therefore, for the first time, we have identified and emphasized that circ_SMA4 is significantly upregulated and plays an oncogenic role in GISTs by sponging miR-494-3p to activate the KIT/JAK/STAT pathway. These findings underscore circ_SMA4 may serve as a novel diagnostic biomarker and therapeutic target for GISTs.

No abstract available

Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.

This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.

Subsequently, a splenic-sparing distal pancreatectomy was performed, followed by immediate imatinib therapy...When encountering a newly developed lesion in a distant organ, surgeons must consider the possibility of metastasis to guide therapeutic decision-making. Early diagnosis and appropriate intervention are paramount, particularly in the case of PGIST, given its infrequent presentation and clinical complexities.

The N-terminal cap of GPR20 functions like an agonist and mediates long-range activated conformational shift. Together with the previous study, this study enhances our knowledge of the self-activation mechanism of the orphan receptor, facilitates the drug discovery efforts that target GPR20.

Sarcomas exhibit a high degree of defects in APM components, with differences among histotypes and tumoral areas. The most commonly altered APM components were HLA Class I subunit β2-microglobulin, HLA Class I subunit α (HC10), and MHC I transporting unit TAP2. The loss of APM components was prognostic of DM and OS and clinically relevant for LMS and DDLPS. This study explores sarcoma molecular mechanisms, enriching personalized therapeutic approaches.

Distinguishing SFT from other tumors was pivotal. Correcting misdiagnoses of tumor type initially and of recurrence later was necessary for appropriate treatment of the correct desmoid type.