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.

1 day ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • RUNX1 (RUNX Family Transcription Factor 1) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1)

KIT mutation

The role of RAS mutations in leukemia progression, differentiation, and drug resistance. (PubMed, Leuk Res Rep)

Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.

4 days ago

Review • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • BCL2L1 (BCL2-like 1) • RAS (Rat Sarcoma Virus) • CEBPA (CCAAT Enhancer Binding Protein Alpha)

KRAS mutation • NRAS mutation • FLT3-ITD mutation • KIT mutation • RUNX1 mutation • RAS mutation • MLL rearrangement • MLL mutation

Venclexta (venetoclax)

StrateGIST 1: First-in-human Study of IDRX-42 in Participants With Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov)

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

6 days ago

Trial completion date • Trial primary completion date • First-in-human

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation

sunitinib • velzatinib (GSK6042981)

Small bowel GIST harboring concurrent KIT exon 9 duplication and SDHC mutation: A case report. (PubMed, Oncotarget)

Activating mutations in KIT or PDGFRA characterize most GISTs and confer sensitivity to imatinib, whereas succinate dehydrogenase (SDH)–deficient GISTs lack these mutations and are typically imatinib resistant...Pathology demonstrated spindle cell GIST with significant treatment effect and retained SDHB expression. This case suggests that oncogenic KIT signaling may remain the dominant driver of GIST behavior despite the presence of a germline SDHC mutation and highlights the importance of integrated molecular interpretation in GIST management.

6 days ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHC (Succinate Dehydrogenase Complex Subunit C)

KIT mutation • KIT exon 9 mutation • PDGFRA mutation

imatinib

Targeting the Unmet Need in Gastrointestinal Stromal Tumors: A Contemporary Review of Investigational Clinical Trials and Therapeutic Landscape. (PubMed, Pharmaceuticals (Basel))

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.

6 days ago

Review • Journal • IO biomarker

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA mutation

imatinib

Genomic profiling and therapeutic targets of Thai melanoma revealed by next-generation sequencing. (PubMed, Sci Rep)

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.

7 days ago

Journal • Next-generation sequencing

BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase)

BRAF V600E • BRAF V600 • KIT mutation • RAS mutation

Oncomine™ Comprehensive Assay Plus

11d

Anti-PD-1 matches interferon as adjuvant therapy for acral melanoma: a retrospective study. (PubMed, Ther Adv Med Oncol)

Adjuvant anti-PD-1 therapy provides RFS comparable to that of HDI in AM and CM, with a superior safety profile. Patients with AM harboring KIT mutations derive greater benefits from adjuvant anti-PD-1 therapy.

11 days ago

Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase)

BRAF mutation • KIT mutation

13d

Stemness and Survival: CD117+/CD133+ Subpopulations Sustain PI3K Signaling and Drive Imatinib Resistance in Head and Neck Mucosal Melanoma. (PubMed, Cells)

The KIT signal to the PI3K signaling pathway does not result exclusively from a KIT mutation localized to Exon 17, but can also be triggered by mutations localized to Exons 11 and 13. In the present study, we identify and characterize an HNMM subpopulation with stemness properties in patients with c-Kit wild-type and mutation, and demonstrate for the first time the mechanisms by which the CD117+/CD133+ HNMM subpopulations survive and confer resistance to the specific inhibitor of c-Kit mutation.

13 days ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase) • CD20 (Membrane Spanning 4-Domains A1)

KIT mutation

imatinib

16d

MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)

P2, N=455, Recruiting, Centre Leon Berard | Trial completion date: Nov 2026 --> Oct 2027 | Trial primary completion date: Feb 2026 --> Oct 2026

16 days ago

Trial completion date • Trial primary completion date

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF mutation • NRAS mutation • BRAF V600 • KIT mutation • CDKN2A deletion • HRAS mutation • KRAS G12 • PDGFRA mutation • KRAS amplification • NRAS G12

Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)

17d

Micro-GIST with BRAF mutation arising in a Leiomyoma: a rare case report and literature review. (PubMed, Z Gastroenterol)

The patient remained in a satisfactory condition post-surgery. This case report describes the first documented micro-GIST with a BRAF mutation arising in a leiomyoma, highlighting the importance of molecular detection in the differential diagnosis of GISTs.

17 days ago

Review • Journal

BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

BRAF mutation • KIT mutation • PDGFRA mutation

18d

Robotic Duodenal Sleeve Resection for Gastrointestinal Stromal Tumor with Rare Exon 8 KIT Mutation Following Neoadjuvant Imatinib. (PubMed, J Vis Exp)

Given the rarity of exon 8 KIT mutations in GISTs, this mutation is not included in standard genetic panels. Although further study is needed, this case suggests that exon 8-mutant GISTs may respond to TKIs, potentially enabling less extensive surgical resection.

18 days ago

Journal

KIT (KIT proto-oncogene, receptor tyrosine kinase)

KIT mutation

imatinib

23d

KQB198 in Combination With Imatinib in Participants With Advanced/Metastatic GIST in 1st Line Setting (clinicaltrials.gov)

P2, N=46, Recruiting, Kumquat Biosciences Inc. | Not yet recruiting --> Recruiting

23 days ago

Enrollment open

KIT (KIT proto-oncogene, receptor tyrosine kinase)

KIT mutation

imatinib