P4, N=30, Not yet recruiting, The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

We report a case of a 60-year-old male who developed intra-abdominal desmoid tumors five years after undergoing laparoscopy and endoscopy cooperative surgery (LECS) for gastric GIST, followed by adjuvant imatinib therapy...Histopathological confirmation remains crucial for accurate diagnosis. Surgical resection is the primary treatment for symptomatic desmoid tumors, but given their high recurrence rate, long-term follow-up and a multidisciplinary approach are essential for optimal management.

Surveillance MRI at 3 months postoperatively revealed local recurrence, prompting combination therapy with sunitinib (VEGF inhibitor) and sintilimab (anti-PD-1 antibody). Follow-up imaging demonstrated significant regression at 1 month, with no evidence of disease progression at 12-month reassessment.

Importantly, PRKAB2 overexpression significantly restored sensitivity to tyrosine kinase inhibitors (TKIs) in sunitinib-resistant RCC cells...Overall, our findings identify PRKAB2 as a critical tumor suppressor in RCC, regulating both protein-protein interactions and lipid metabolism to suppress mitophagy. Targeting PRKAB2-associated pathways may provide a promising therapeutic strategy to enhance treatment efficacy and overcome drug resistance in RCC.

These NETs facilitate tumor cell migration and adhesion while conferring resistance to tyrosine kinase inhibitors (sunitinib and sorafenib) and anti-PD-1 therapy. In vivo, the treatment with DNase1 to disrupt NETs effectively reversed this therapeutic resistance. Our findings unveil the miR-301b-3p/ITPKB/PARP1/IL8/NETs axis as a novel mechanistic link between tumor-intrinsic signaling and neutrophil-driven immunosuppression, providing a solid experimental foundation for developing combination therapeutic strategies for advanced ccRCC.

PDGFRB was validated as a core node within the PTMRS network: activation of PDGFRβ in human colonic fibroblasts promoted CRC cell proliferation and migration, whereas sunitinib attenuated and reversed these effects...These findings suggest that PTMRS may help identify patients who could benefit from combining immunotherapy with therapies targeting PDGFRβ or other PTM-related pathways. Further validation in in vivo models and prospective clinical cohorts is needed.

Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML.

This allowed for targeted therapy with a tyrosine kinase inhibitor (TKI), leading to molecular remission monitored by RT-qPCR. This case highlights how a multidisciplinary approach can identify atypical transcripts in MPN, guiding targeted therapy with TK inhibitors, thus resulting in effective treatment and molecular remission.

The remaining patient had an unresectable tumor and received tyrosine kinase inhibitor therapy; however, sequential treatment with imatinib and sunitinib was clinically ineffective. However, their clinical behavior differs: D842Y-mutant GISTs consistently present as large, hypervascular tumors associated with acute complications. The therapeutic efficacy of tyrosine kinase inhibitors remains unclear, underscoring the need for further case accumulation to better define the clinical course and determine optimal treatment strategies for this rare subtype.

Several conjugates, particularly 3a (87.47 %) and 3 g (96.62 %) in MCF-7, induced late apoptosis, and 3c (98.57 %) in MDA-MB-231 induced the highest early apoptosis. Across both proteins (3G0E and 4AGD), 3c consistently shows stronger predicted binding than sunitinib, with more negative binding energies and lower Ki values in each case, supporting its promise as a lead together with 3a.

Imatinib and rosuvastatin were discontinued, and the patient was managed with intravenous fluids and supportive care. This case represents one of the most severe reported instances of imatinib-induced rhabdomyolysis. Early recognition and discontinuation are essential to prevent life-threatening sequelae.

This study offers valuable insights into the safety and feasibility of imatinib discontinuation for patients with CML, supporting long-term remission while maintaining survival. This study was registered at ClinicalTrials.gov as #NCT00478985.