KIT (KIT proto-oncogene, receptor tyrosine kinase)

Strong agreement: it is recommended to perform systematic regional and remote extension assessment at diagnosis; PET-CT is the gold standard for remote assessment; isolated radiotherapy is not recommended for curative treatment; given the major risk of metastasis and the poor prognosis, alternatives to heavy destructive surgery should be considered in the rare cancer multidisciplinary tumor board; it is recommended to screen for NRAS, BRAF and KIT mutations, to identify possible treatment targets; reference imaging should be performed 3 months after end of treatment, using sinonasal and brain MRI and PET-CT; due to the risk of early recurrence, close follow-up is recommended during the first 2 years, then at least every 6 months up to 5 years postoperatively. Relative agreement: operable sinonasal mucosal melanoma should be treated by total macroscopic resection with negative margins followed by radiotherapy on the tumor bed; postoperative radiotherapy is recommended, to improve local control; neoadjuvant or adjuvant chemotherapy, other than immunotherapy or targeted therapy, is not recommended; for non-resectable and/or metastatic sinonasal mucosal melanoma, immunotherapy is the systematic first-line treatment; prophylactic lymph-node treatment is not recommended in N0 sinonasal mucosal melanoma; lymph-node surgery is recommended in N+ cases without remote metastasis, including cases of regional recurrence.

Our findings suggest that non-D816 KIT mutations are associated with a less aggressive clinical phenotype, lower mast-cell differentiation, and improved outcomes. These results support a biologically distinct role of non-D816 KIT variants in MNs and highlight the need for refined risk stratification incorporating KIT variant classes.

Long-term organ culture recapitulates key molecular features of fibroids and reveals tissue-specific mechanisms governing stem cell activation and differentiation. These findings identify potential therapeutic opportunities and establish long-term organ culture as a robust, physiologically relevant platform for investigating normal and tumor biology.

Furthermore, in immunocompromised mice engrafted with an advSM-like MC cell line, repetitive applications of anti-CD117-CAR T-cells were able to inhibit MC expansion. These data may pave the way for the development of anti-CD117-CAR T-cell therapies in advSM.

When FGF1 was knocked down in DRGs, SCF-mediated nerve sprouting was prevented. Taken together, our studies demonstrate the importance of the SCF/c-Kit axis in CIBP and nerve sprouting, and identify the SCF/c-Kit/FGF1 pathway as a potential therapeutic target for CIBP.

P1, N=278, Recruiting, IDRX, Inc., a wholly owned subsidiary of GSK, LLC | Trial completion date: Nov 2027 --> Jun 2028 | Trial primary completion date: Nov 2027 --> Mar 2027

Owing to their rarity and small size, appendiceal GISTs are often discovered incidentally and may present diagnostic challenges. Herein, we report a rare case of appendiceal GIST detected preoperatively and successfully treated by laparoscopic appendectomy, with long-term recurrence-free survival.

The patient recovered uneventfully and was started on treatment with imatinib mesylate...GISTs should be considered in cases of unexplained SBV. This case emphasizes the diagnostic challenges, the need for prompt surgical palliation, and the role of systemic tyrosine kinase inhibitors in advanced presentation of GIST.

Although tyrosine kinase inhibitors (TKIs), particularly imatinib, have substantially improved outcomes, most patients with advanced disease eventually develop resistance, resulting in disease progression...Molecular stratification and personalized approaches dominate ongoing research, but evidence generation remains limited by small sample sizes and slow recruitment. Future trials integrating innovative therapeutic platforms and patient-centered outcomes are essential to improve long-term disease control and quality of life.

A secondary objective was to assess whether mRNA expression levels of the endoplasmic reticulum (ER) stress sensors X-box-binding protein 1 (uXBP1) and activating transcription factor 6 (ATF6), and the chaperone-mediated autophagy marker Lysosomal-Associated Membrane Protein 2 (LAMP2A) by droplet digital PCR (ddPCR), were associated with resistance to the second-generation proteasome inhibitor (PI) carfilzomib (Cfz)...Samples were obtained as part of standard clinical care and/or during treatment with Bortezomib (Btz) or Cfz...Cfz adaptation was associated with reduced levels of uXBP1 and LAMP2A mRNA in MM cell lines. Future prospective studies evaluating the clinical utility of ER stress and chaperone-mediated autophagy associated transcripts in CPCs as predictors of resistance to PI are warranted.

Notably, patients harboring KIT mutations showed a trend toward shorter disease-free survival, suggesting a potential prognostic role that warrants further investigation. These findings provide initial genomic understanding of Thai melanoma and highlight candidate actionable mutations for future precision oncology research.

Particularly, the detection sensitivity for NTRK3 fusions was significantly enhanced and reached 95.89 %. This study contributes to clarifying NTRK fusion distribution in patients and validates a standardized, sensitive pan-TRK IHC strategy for clinical screening.