PDGFRA mutation

Resistance to drugs in sarcoma is multifactorial and changeable. Nevertheless, fusing mechanistic knowledge with biomarker - guided combination/sequential therapies offers a clear way to improve patient situations.

Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs)...These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

In this study, targeted next-generation sequencing using the AmpliSeq for Illumina Cancer HotSpot Panel identified pathogenic mutations in canonical cancer driver genes: tumor protein p53 (TP53) NM_000546.6:c.730G>T (p.Gly244Cys) and platelet-derived growth factor receptor alpha (PDGFRA) NM_006206.6:c.2525A>T (p.Asp842Val) mutations in renal leiomyosarcoma and NRAS proto-oncogene, GTPase (NRAS) NM_002524.5:c.35G>T (p.Gly12Val) mutation in the ovarian tumor. These findings suggest a potential benefit of personalized therapies for XP patients with internal malignancies.

The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.

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