PDGFRA mutation

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027

Targeted therapies for PDGFRA and PIK3CA mutations control tumor growth but face drug resistance and cost issues. This study provides a new theoretical basis and treatment strategy for cervical cancer, guiding future research.

Endoscopic techniques offer advantages for deep-seated lesions by minimizing cortical damage while allowing adequate tumor resection. Further studies are needed to establish the optimal treatment strategies and clarify the long-term prognosis of myxoid glioneuronal tumor.

Treatment with imatinib, a tyrosine kinase inhibitor, resulted in a continuous complete molecular response (CMR). To our knowledge, this is the first report to demonstrate the clinical and cytogenetic manifestations of BCR::PDGFRA positive myeloid neoplasm coexisting PDGFRA mutations. Furthermore, it emphasizes the effectiveness of targeted therapy and the significance of personalized management.

Neoadjuvant imatinib has been increasingly adopted for locally advanced or anatomically complex tumors to facilitate resectability and organ preservation, although optimal treatment duration and patient selection remain controversial...Nevertheless, duodenum-specific data remain limited, and consensus on optimal management strategies is lacking. This review summarizes current evidence and evolving strategies in the diagnosis and treatment of dGISTs, with a focus on surgical decision-making, perioperative systemic therapy, and ongoing clinical trials, and highlights critical unmet needs requiring future investigation.

P1/2, N=58, Completed, Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy | Active, not recruiting --> Completed

The introduction of imatinib, a selective tyrosine kinase inhibitor (TKI), revolutionized the management of advanced GIST...Current approaches emphasize molecular subtype-guided first-line therapy, ctDNA-driven sequencing of subsequent lines, and the use of novel TKIs (e.g., avapritinib, ripretinib, bezuclastinib) tailored to specific resistance mutations. Furthermore, we explore emerging modalities such as boron neutron capture therapy (BNCT), which offers a kinase-independent mechanism to target resistant disease, and combination strategies that integrate immunotherapy, epigenetic modulators, and pathway-specific inhibitors. Advances in liquid biopsy and molecular profiling are enabling real-time adaptation of therapy, moving GIST management toward a dynamic, personalized paradigm aimed at overcoming resistance and improving patient outcomes.

P2, N=28, Recruiting, Reema A. Patel | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

These tumors express diagnostic GIST markers (c-Kit and DOG1) and show significant response to the BRAF inhibitor dabrafenib. This model recapitulates key histopathological and molecular features of human BRAF-mutant GIST and provides a valuable platform for studying tumor initiation, progression, and therapeutic resistance. Importantly, it allows for preclinical testing of targeted therapies in BRAF GIST, offering new insights into treatment strategies.

For therapeutic categories, performance reached 0.84 for avapritinib sensitivity, 0.81 for imatinib sensitivity. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably to established risk scores across international cohorts, providing a baseline for future multimodal predictors. Deep learning on histology predicts KIT and PDGFRA mutations in a large international cohort of GISTs from multiple centers Whole-slide image models stratify recurrence-free survival comparable to pathology-based risk scores Prognostic value of deep learning is preserved in adjuvant therapy subgroups, supporting treatment duration decisions.

Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care.

These cases underscore the importance of interpreting SDHA variants carefully, as the identification of germline SDHA variants does not always indicate the need for aggressive surveillance or intervention. Germline SDHA variants increase the risk of PPGLs and wild-type GISTs.The penetrance of germline SDHA variants in carriers without an SDHA-related tumour is low.Careful clinical assessment is essential to determine if a patient with an SDHA germline mutation has an SDHA-related tumour.This is particularly complex in GISTs, as only wild-type GISTs (those without somatic variants in c-Kit or PDGFRA) are likely to be SDHA-related.Immunohistochemistry for expression of SDH subunits can help clarify whether a tumour is related to SDHA variants.