News - PDGFRA mutation

Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015) (clinicaltrials.gov)

P2, N=322, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2027 --> Jun 2029 | Trial primary completion date: Feb 2027 --> Jun 2029

9 days ago

Trial completion date • Trial primary completion date • Stroma • Metastases

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • VHL (von Hippel-Lindau tumor suppressor) • EPAS1 (Endothelial PAS domain protein 1)

PDGFRA mutation

Welireg (belzutifan)

ALT GIST: A Randomised Trial of Imatinib Alternating With Regorafenib Compared to Imatinib Alone for the First Line Treatment of Advanced Gastrointestinal Stromal Tumour (GIST) (clinicaltrials.gov)

P2, N=78, Completed, Australasian Gastro-Intestinal Trials Group | Active, not recruiting --> Completed

9 days ago

Trial completion • Stroma • Metastases

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ANO1 (Anoctamin 1)

PDGFRA mutation

imatinib • Stivarga (regorafenib)

12d

Are PDFGRA Dinucleotide Alterations Definitional for Myxoid Glioneuronal Tumor? Report of PDFRA p. K385L Mutation in a Neonatal High-Grade Glioma. (PubMed, Pediatr Dev Pathol)

In summary, we report the occurrence of PDGFRA hotspot mutation in a neonatal high-grade glioma without distinct features of MGNT, demonstrating that this genetic alteration is not specific to MGNT. We recommend caution in classifying a tumor as MGNT solely by the presence of PDGFRA alteration.

12 days ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

17d

Prognostic Significance of C-MYC and EGFR Overexpression in Gastrointestinal Stromal Tumors: An Immunohistochemical Study. (PubMed, Appl Immunohistochem Mol Morphol)

Our findings suggest that both C-MYC and EGFR may be overexpressed and/or amplified in GISTs, indicating their potential prognostic role. This could also pave the way for therapeutic strategies targeting these proteins.

17 days ago

Journal • Stroma

EGFR (Epidermal growth factor receptor) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

EGFR expression • KIT mutation • MYC expression • PDGFRA mutation

Longitudinal detection of somatic mutations in the saliva of head and neck squamous cell carcinoma-affected patients: a pilot study. (PubMed, Front Oncol)

Our data indicate that sDNA could aid in the monitoring of patients' follow-up as low-frequency somatic mutations could be assessed from the saliva of HNSCC patients. Prospectively, these results suggest that salivary-based liquid biopsy might pave the way for personalized molecular therapies based on mutational data.

1 month ago

Journal

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • PDGFRA mutation

Different efficacy of tyrosine kinase inhibitors by KIT and PGFRA mutations identified in circulating tumor DNA for the treatment of refractory gastrointestinal stromal tumors. (PubMed, BJC Rep)

ctDNA-based analysis facilitates assessment of disease status and genomic profiles, thus potentially assisting in identifying optimal therapeutic strategies for advanced GIST patients.

1 month ago

Journal • Circulating tumor DNA • Stroma

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

KIT mutation • PDGFRA mutation

A Study of DCC-3116 in Combination with Anticancer Therapies in Participants with Advanced Malignancies (clinicaltrials.gov)

P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029

1 month ago

Trial completion date

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

BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation

Qinlock (ripretinib) • inlexisertib (DCC-3116)

2ms

Gastrointestinal Stromal Tumors: Variants and Some Pitfalls That They Create. (PubMed, Adv Anat Pathol)

It is also important to consider morphologic and immunophenotypic changes associated with treatment, including the potential absence of kit expression, particularly in GISTs that have metastasized. Therefore, obtaining clinical information regarding prior therapy with a tyrosine kinase inhibitor (TKI) is crucial.

2 months ago

Review • Journal • Stroma

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • ANO1 (Anoctamin 1)

PDGFRA mutation • KIT expression

2ms

Comprehensive Genomic Assessment of Advanced-Stage GI Stromal Tumors Using the Japanese National Center for Cancer Genomics and Advanced Therapeutics Database. (PubMed, JCO Precis Oncol)

This study highlights the genomic landscape of advanced GISTs and the important role of CGP in identifying rational molecular-targeted therapeutic options.

2 months ago

Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker • Stroma • Metastases

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • NTRK (Neurotrophic receptor tyrosine kinase) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TMB-H • NTRK3 fusion • HRD • ETV6-NTRK3 fusion • PDGFRA mutation • PDGFR wild-type

Keytruda (pembrolizumab)

2ms

Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update. (PubMed, Curr Treat Options Oncol)

Despite the significant improvement in treatment outcomes with adjuvant imatinib therapy for patients, drug resistance remains a major challenge for GIST therapy...The OXPHOS pathway is a promising therapeutic target in combination with TKI against sensitive KIT/PDGFRA mutants. Comprehensive understanding of the above resistance mechanisms, experimental drugs/strategies and metabolic changes is critical to implement the proper therapy strategy and improve the clinical therapy outcomes for GIST.

2 months ago

Review • Journal • Stroma

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

PDGFRA mutation

imatinib

2ms

Molecular profiling of Oral epithelial dysplasia and Oral Squamous cell carcinoma using Next Generation Sequencing. (PubMed, J Stomatol Oral Maxillofac Surg)

The results obtained in this study explain the diverse genetic mutations in various grades of oral squamous cell carcinoma. Identification of these mutations would help in providing better treatment, designing a proper treatment plan for the patients with OSCC and support minimal intervention medicine.

2 months ago

Journal • Next-generation sequencing

NRAS (Neuroblastoma RAS viral oncogene homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7)

TP53 mutation • NRAS Q61 • CTNNB1 mutation • PDGFRA mutation • NRAS G13 • TP53 R248Q • TP53 R213

2ms

Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada. (PubMed, Ther Adv Med Oncol)

This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

2 months ago

Review • Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

imatinib • sunitinib • Stivarga (regorafenib) • Ayvakit (avapritinib) • Qinlock (ripretinib)

2ms

MicroRNA expression signature in gastrointestinal stromal tumour & their molecular & histological features. (PubMed, Indian J Med Res)

Interpretation & conclusions The present study showed that the down-regulation of these miRNAs may help better molecular classification and characterization of GISTs. Our results offer new insight into the association between miRNAs and histological features, enabling a more thorough understanding of GISTs at the molecular level.

2 months ago

Journal • Stroma

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MIR34A (MicroRNA 34a-5p) • MIR221 (MicroRNA 221) • MIR494 (MicroRNA 494) • MIR222 (MicroRNA 222)

KIT exon 11 mutation • PDGFRA mutation • KIT expression

3ms

Clinicopathological and Molecular Genetic Insights into EBV-Positive Inflammatory Follicular Dendritic Cell Sarcoma. (PubMed, Hum Pathol)

Compared with the FDCS group, EBV+ IFDCS patients had a significantly longer median PFS time (p<0.05). In conclusion, EBV+ IFDCS represents a group of tumors with unique clinical, morphological, immunological, prognostic, and molecular cytogenetic characteristics.

3 months ago

Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • MTHFR (Methylenetetrahydrofolate Reductase) • SSTR2 (Somatostatin Receptor 2) • NQO1 (NAD(P)H dehydrogenase, quinone 1) • FANCG (FA Complementation Group G) • CDKN1C (Cyclin Dependent Kinase Inhibitor 1C) • CR1 (Complement C3b/C4b Receptor 1) • FCER2 (Fc Fragment Of IgE Receptor II)

EGFR expression • PDGFRA mutation • MSH2 mutation • MLH1 mutation • STAT3 expression • FANCG mutation

3ms

Oncogenetic Panel and Integrated Clinical Data Registry Study for Wild Type Gastrointestinal Stromal Tumor Patients (clinicaltrials.gov)

P=N/A; Trial primary completion date: Dec 2025 --> Dec 2024

3 months ago

Trial primary completion date • Stroma

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

PDGFRA mutation • KIT wild-type • PDGFR wild-type

OncoPanel™ Assay

3ms

Two different mutational types of familial gastrointestinal stromal tumors: Two case reports. (PubMed, World J Gastrointest Oncol)

Different mutation types of familial GISTs in the same family are very rare, thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.

3 months ago

Journal • Stroma

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

KIT mutation • PDGFRA mutation

imatinib

3ms

BLU-285-3101: A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling (clinicaltrials.gov)

P1/2, N=37, Active, not recruiting, Blueprint Medicines Corporation | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Dec 2025

3 months ago

Enrollment closed • Trial completion date

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

PDGFRA mutation

Ayvakit (avapritinib)

3ms

Demographic Trends, Coalterations, and Imatinib Resistance across Genomic Variants in Gastrointestinal Stromal Tumors: An AACR Project GENIE Analysis. (PubMed, Oncology)

Sex and race/ethnic differences in genomic alterations, as well as co-mutations, were prevalent among patients with GIST. Variations in mutational profiles highlight the importance of distinct genetic drivers that may be targeted to treat different patient populations.

3 months ago

Journal • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MTAP (Methylthioadenosine Phosphorylase)

PDGFRA mutation

imatinib • sunitinib • Qinlock (ripretinib)

3ms

Integrated analyses reveal two molecularly and clinically distinct subtypes of H3 K27M-mutant diffuse midline gliomas with prognostic significance. (PubMed, Acta Neuropathol)

However, all significant parameters tested were dependent on the cluster attribution, which had the largest effect on survival: DMG-A had a significantly better survival compared to DMG-B (p < 0.001). Hence, the subtype attribution based on two methylation clusters can be used to predict survival as it integrates different molecular and clinical parameters.

3 months ago

Journal

TP53 (Tumor protein P53) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

TP53 mutation • PDGFRA mutation

4ms

Managing locally advanced GIST complicated by perforation: A case report and comprehensive review. (PubMed, Radiol Case Rep)

The prognosis of GIST varies widely, with localized tumors having favorable outcomes following resection, while metastatic cases often face a poorer prognosis despite advances in targeted therapies. This case exemplifies the critical need for personalized treatment plans and ongoing research to improve the management and prognosis of GIST patients.

4 months ago

Review • Journal • Metastases

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ANO1 (Anoctamin 1)

KIT mutation • PDGFRA mutation

5ms

Role of PIK3CA as a predictive biomarker in metastatic, imatinib-resistant GIST: A ct-DNA substudy of the VOYAGER trial (ESMO 2024)

Background: The VOYAGER-trial compared avapritinib (ava) with regorafenib (rego) in patients (pts) with advanced gastrointestinal stromal tumors (GIST) in a 3rd-line setting. In a 3rd-line setting, pathogenic PIK3CA mutations represent the most common genomic event in an oncogenic KIT signaling intermediate but were found in only 4.7% of pts using ctDNA sequencing. The presence of PIK3CA mutations in plasma did not preclude prolonged disease control to ava or rego. Limitations of this analysis are the small sample size and the possibility of clonal hematopoiesis of indeterminate potential (CHIP) as PIK3CA mutations were not confirmed in tumor samples.

5 months ago

Circulating tumor DNA • Metastases

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PIK3CA mutation • KIT mutation • PDGFRA mutation • KIT T670I • PIK3CA H1047L • KIT A829P

Guardant360® CDx

imatinib • Stivarga (regorafenib) • Ayvakit (avapritinib)

7ms

Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))

Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.

7 months ago

Journal • Next-generation sequencing • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type

imatinib

8ms

Monitoring advanced gastrointestinal stromal tumor with circulating tumor DNA. (PubMed, Curr Opin Oncol)

The dynamic field of ctDNA technologies is rapidly evolving and holds significant promise for research. Several trials have successfully validated the clinical utility of ctDNA in metastatic GIST, laying the foundations for its prospective integration into the routine clinical management of GIST patients.

8 months ago

Clinical • Journal • Circulating tumor DNA • Stroma • Metastases

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

8ms

ETV6::NTRK3 Fusion-Positive Wild-Type Gastrointestinal Stromal Tumor (GIST) with Abundant Lymphoid Infiltration (TILs and Tertiary Lymphoid Structures): A Report on a New Case with Therapeutic Implications and a Literature Review. (PubMed, Int J Mol Sci)

The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

8 months ago

Clinical • Observational data • Retrospective data • Review • Journal • IO biomarker • Stroma

KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ETV6 (ETS Variant Transcription Factor 6) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TFG (Trafficking From ER To Golgi Regulator) • NTRK (Neurotrophic receptor tyrosine kinase) • ANO1 (Anoctamin 1)

NTRK3 fusion • RB1 mutation • PDGFRA mutation • NTRK3 positive • NTRK fusion

Rozlytrek (entrectinib)

9ms

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

P1, N=240, Recruiting, IDRx, Inc. | N=143 --> 240

9 months ago

Enrollment change • Stroma • Metastases

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • PDGFRA mutation • PDGFRA exon 18 mutation

sunitinib • IDRX-42

9ms

Imatinib TDM in GIST (clinicaltrials.gov)

P2, N=28, Recruiting, Reema A. Patel | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2024 --> Dec 2025

9 months ago

Enrollment open • Trial primary completion date • Stroma

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

KIT mutation • PDGFRA D842V • PDGFRA mutation

imatinib

9ms

PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling. (PubMed, Sci Rep)

Furthermore, we evaluated the sensitivity of these mutants to three FDA-approved tyrosine kinase inhibitors: imatinib, dasatinib, and avapritinib, which effectively suppressed the constitutive activity of the mutant receptors. Interestingly, K385M was reported in a few cases of brain tumors but not in MGNT. Our results provide valuable insights into the molecular mechanism underlying the activation of PDGFRα by the K385I/L mutations, highlighting their potential as actionable targets in the treatment of myxoid glioneuronal tumors.

9 months ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

dasatinib • imatinib • Ayvakit (avapritinib)

10ms

Gastrointestinal stromal tumors in fine-needle aspiration biopsies. (PubMed, Diagn Cytopathol)

Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.

10 months ago

Journal • Stroma • Biopsy

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CD34 (CD34 molecule) • ANO1 (Anoctamin 1)

PDGFRA mutation

10ms

Mutational Landscape and Clinicopathologic Features of Plasmablastic Lymphoma (USCAP 2024)

In conclusion, our findings shed light on the unique molecular complexity of PBL, unveiling its mutational landscape and potential therapeutic targets. Due to the rarity of PBL, further research with a more extensive sample size is essential to completely elucidate the mutational landscape of PBL.

10 months ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TNFRSF8 (TNF Receptor Superfamily Member 8) • STAT3 (Signal Transducer And Activator Of Transcription 3) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • SDC1 (Syndecan 1) • TCF3 (Transcription Factor 3) • CCND3 (Cyclin D3) • CD79A (CD79a Molecule) • TNFRSF13B (TNF Receptor Superfamily Member 13B)

KRAS mutation • KRAS G12V • MYD88 mutation • KRAS G12 • KRAS G13 • PDGFRA mutation • STAT3 mutation

Archer® FusionPlex® Lymphoma

10ms

DS-6157a in Participants With Advanced Gastrointestinal Stromal Tumor (GIST) (clinicaltrials.gov)

P1, N=34, Terminated, Daiichi Sankyo | Completed --> Terminated; The study was terminated due to a business decision.

10 months ago

Trial termination • Stroma • Metastases

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • GPR20 (G Protein-Coupled Receptor 20)

KIT mutation • PDGFRA D842V • PDGFRA mutation

DS-6157

10ms

KIT/PDGFRA inhibitors for the treatment of gastrointestinal stromal tumors: getting to the gist of the problem. (PubMed, Expert Opin Investig Drugs)

Despite the outstanding results of first-line imatinib in advanced GIST, resistance ultimately occurs mainly through secondary mutations in KIT/PDGFRA...However, it is now recognized that the situation is more intricate, with various factors interacting with KIT and PDGFRA, playing a crucial role in the response and resistance to treatments. Future strategies in the management of advanced GIST should integrate driver inhibition with the blockade of other molecules to enhance cell death and establish enduring responses in patients.

10 months ago

Journal • Stroma

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

KIT mutation • PDGFRA mutation

imatinib • Ayvakit (avapritinib) • Qinlock (ripretinib) • IDRX-42 • bezuclastinib (PLX9486)

11ms

Primary Papillary Colonic Adenocarcinoma With PDGFRA Mutation. A New Morphological Subtype? A Case Report and Review of Literature. (PubMed, Int J Surg Pathol)

To the best of our knowledge, there have been only two examples of primary papillary colon carcinoma reported in the literature, and neither of them with a PDGFRA mutation. We describe one tumor and discuss its pathological features.

11 months ago

Review • Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NKX2-1 (NK2 Homeobox 1) • CDX2 (Caudal Type Homeobox 2) • GATA3 (GATA binding protein 3) • PAX8 (Paired box 8)

PDGFRA mutation

11ms

Mutational analysis of PDGFRA oncogene in high-grade neuroendocrine carcinoma of the uterine cervix in twelve Taiwanese women. (PubMed, Taiwan J Obstet Gynecol)

No abstract available

11 months ago

Journal

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

12ms

Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor (PubMed, Zhonghua Bing Li Xue Za Zhi)

The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

12 months ago

Journal • Stroma

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation

12ms

Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA. (PubMed, Nat Commun)

Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.

12 months ago

Journal

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

PDGFRA D842V • PDGFRA mutation • PDGFR wild-type

Ayvakit (avapritinib)

12ms

Sarco/endoplasmic reticulum calcium ATPase 3 (SERCA3) expression in gastrointestinal stromal tumours. (PubMed, Pathology)

In conclusion, SERCA3 immunohistochemistry may be useful for the diagnosis of GIST with high confidence, when used as a third marker in parallel with KIT and DOG1. Moreover, SERCA3 immunopositivity may be particularly helpful in cases with negative or weak KIT or DOG1 staining, a situation that may be encountered de novo, or during the spontaneous or therapy-induced clonal evolution of GIST.

12 months ago

Journal • Stroma

KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ANO1 (Anoctamin 1)

PDGFRA mutation

12ms

Genomic profiling in GIST: Implications in clinical outcome and future challenges. (PubMed, Neoplasia)

Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.

12 months ago

Clinical data • 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 • KIT exon 11 mutation • KIT exon 9 mutation • PDGFRA mutation

imatinib • sunitinib • Ayvakit (avapritinib)

12ms

Molecular and clinicopathological features of KIT/PDGFRA wild-type gastrointestinal stromal tumors. (PubMed, Cancer Sci)

NF1-GISTs involved multifocal spindle cell tumors in the small intestine. SDH-GISTs occurred in young patients and were multifocal in the stomach and clinically indolent.

12 months ago

Journal • Stroma

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

TP53 mutation • BRAF V600E • BRAF V600 • NF1 mutation • CHEK2 mutation • PDGFRA mutation • SDHB mutation • PDGFR wild-type

12ms

Site specific genetic differences in colorectal cancer via Next-Generation-Sequencing using a multigene panel. (PubMed, Ann Ital Chir)

The utility of actionable multigene panel revealed the value of a well-designed next-generation sequencing workflow in the practical use of clinical outcomes via the prediction of responsiveness to therapeutic agents or indications for novel treatment modalities in addition to prognosis estimate.

12 months ago

Journal • Next-generation sequencing

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • KIT mutation • PDGFRA mutation

Erbitux (cetuximab) • Vectibix (panitumumab)

1year

Multifocal gastrointestinal stromal tumor with osseous metaplasia: a case report. (PubMed, J Med Case Rep)

In conclusion, osseous metaplasia in GIST is a very rare event and only few cases are reported in the literature. The number of reported cases is inadequate to confirm the pathogenesis and the prognosis.

1 year ago

Journal • Stroma

PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

PDGFRA mutation • PDGFRA exon 12 mutation

1year

"De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade. (PubMed, Acta Neuropathol)

The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

1 year ago

Journal • Checkpoint inhibition • Checkpoint block

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

TP53 mutation • EGFR amplification • PTEN mutation • NF1 mutation • CDKN2A deletion • CDKN2A mutation • PDGFRA mutation • TERT mutation • IDH wild-type • TERT promoter mutation

1year

AML with t(4; 12)(q12; p13): A Detailed Genomic and Transcriptomic Analysis Reveals Genomic Breakpoint Heterogeneity, Absence of Pdgfra Fusion Transcripts and Presence of Pdgfra Overexpression in a Subset of Cases (ASH 2023)

Analysis of AML with t(4; 12)(q12; p13) translocation by WGS and WTS provides detailed information that separates two subsets distinguished by distinct breakpoint cluster regions on 4q12 and PDGFRA gene expression. The clinical impact of increased PDGFRA gene expression on response to TKI and prognosis as well as the presence of additional fusion transcripts has to be evaluated in further studies.

1 year ago

Clinical • Omic analysis

BCR (BCR Activator Of RhoGEF And GTPase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ASXL1 (ASXL Transcriptional Regulator 1) • ETV6 (ETS Variant Transcription Factor 6) • ADAMTS3 (ADAM Metallopeptidase With Thrombospondin Type 1 Motif 3) • SCFD2 (Sec1 Family Domain Containing 2)

ASXL1 mutation • PDGFRA mutation • PDGFRA overexpression • PDGFRA fusion