Gastrointestinal Stromal Tumor

This perspective highlights key structural insights that elucidate the molecular basis of resistance and its interplay with kinase activation and TKI binding. A comprehensive understanding of these molecular alterations is crucial for guiding future therapeutic strategies to overcome resistance.

We present two cases of family members affected with multifocal GIST tumors who underwent germline genetic analysis and were found to have germline pathogenic variants in Exon 11 of the KIT gene [c.1735_1737del (p.Asp579del)]. Both patients were treated with Imatinib with good response.

P2, N=24, Not yet recruiting, Dana-Farber Cancer Institute

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.

No adjuvant therapy was administered due to the absence of residual disease and actionable mutations. This case highlights the broad tumor spectrum in NF1 and underscores the importance of comprehensive imaging, multidisciplinary management, and genetic testing for optimal outcomes.

PDE3A plays a pivotal role in tumorigenesis and cancer progression, with aberrant expression strongly associated with tumor proliferation, metastasis, and resistance to chemotherapy. As a therapeutic target, PDE3A holds significant potential. The development of PDE3A inhibitors or molecular adhesive agents may offer novel treatment strategies, particularly for chemotherapy-resistant tumor types.

Although no single cancer fully mirrors PAH, the identification of multiple analogs underscores PAH's multidimensional complexity and confirms its overlap with oncological conditions. Cancer analogs could serve as a valuable framework for enhancing recognition of PAH's clinical, therapeutic, and HRCU implications among healthcare stakeholders.

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.

Here, we review the present knowledge on KIT retention in the Golgi/TGN region in GISTs, molecular mechanisms underlying this retention, and the aberrant localization of other RTK mutants. We also discuss strategies for the medical development of RTK inhibition by blocking intracellular trafficking.

Prognosis depends primarily on tumour location, size and mitotic index. In high-risk cases, adjuvant imatinib therapy is warranted.

In summary, accumulation of succinate in SDH-deficient tumors inhibited KDM4 activity, impaired DNA repair and yielded enhanced susceptibility to Ym155-induced reactive oxygen species (ROS) generation. The identified intrinsic susceptibilities of SDHB-deficient cancers have the potential to be therapeutically leveraged.