News - NF2 negative - LARVOL VERI

10ms

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature. (PubMed, Arch Pathol Lab Med)

Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling...One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

10 months ago

Review • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF2 (Neurofibromin 2) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

CDKN2A mutation • NF2 mutation • NF2 negative

sirolimus

11ms

Case report of selumetinib as a novel therapy in a neurofibromatosis type 2-associated ependymoma. (PubMed, Mol Ther Methods Clin Dev)

Due to progression of all tumors, he was treated medically with both everolimus (10 mg/day) and selumetinib (25 mg/kg twice a day), but he rapidly transitioned to selumetinib monotherapy due to everolimus toxicity. This PR was quantified by the differences in units of intensity in pre- and post-treatment magnetic resonance image. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.

11 months ago

Journal

NF2 (Neurofibromin 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

SMARCB1 mutation • NF2 negative

everolimus • Koselugo (selumetinib)

over1year

First-in-Human Phase 1 Trial of VT3989, a First-in-Class YAP/TEAD Inhibitor in Patients with Advanced Mesothelioma (IASLC-WCLC 2023)

The 44 mesothelioma patients had a median age of 65 (range 21-83), ECOG PS of 0 (n=7) or 1 (n=37), median of 3 prior regimens (range 1-8); all had received prior platinum and pemetrexed, 43/44 (98%) had prior immune checkpoint inhibitors and 16/44 (36%) had VEGF antibodies; 33 had epithelioid, 7 biphasic and 4 sarcomatoid histology. VT3989 is well tolerated with durable responses in patients with refractory mesothelioma. This study provides the first clinical proof-of-concept for drugging the Hippo-YAP-TEAD pathway. RP2D optimization including further schedule evaluation and expansion are ongoing in mesothelioma patients evaluating different intermittent schedules.

over 1 year ago

Clinical • P1 data • IO biomarker • Metastases

NF2 (Neurofibromin 2)

NF2 mutation • NF2 negative

pemetrexed • VT3989

over1year

Atypical meningioma with YAP1-MAML2 fusion: A case report and review of the literature (AANP 2023)

Conclusions We identified a YAP1-MAML2 atypical meningioma with brain invasion located within the brain parenchyma. Larger cohort studies are needed to determine a possible prognostic role of YAP1 alterations in meningiomas.

over 1 year ago

Clinical • Review

CDH1 (Cadherin 1) • YAP1 (Yes associated protein 1) • GFAP (Glial Fibrillary Acidic Protein) • MAML2 (Mastermind Like Transcriptional Coactivator 2)

NF2 negative

almost2years

Branchioma: A Series of 23 Cases Illustrating Frequent Loss of the Retinoblastoma 1 (Rb1) (USCAP 2023)

Recent developments support b ranchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry represents a true pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy samples.

almost 2 years ago

Clinical • BRCA Biomarker

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • PTCH1 (Patched 1) • MSH6 (MutS homolog 6) • KMT2C (Lysine Methyltransferase 2C) • CD34 (CD34 molecule) • PLCG2 (Phospholipase C Gamma 2) • XRCC2 (X-Ray Repair Cross Complementing 2) • TP63 (Tumor protein 63) • FANCG (FA Complementation Group G) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • CHD2 (Chromodomain Helicase DNA Binding Protein 2) • PHOX2B (Paired Like Homeobox 2B)

KRAS A146V • NF2 negative

TruSight Oncology 500 Assay

over2years

FAK inhibitor APG-2449 and CDK4/6 inhibitor palbociclib synergistically suppress mesothelioma tumor growth via autophagy induction (AACR 2022)

The synergistic effects are evidently mediated by induced autophagy and enhanced cellular senescence. This preclinical study lays a foundation for future clinical development of APG-2449 combined with CDK4/6 inhibitors for mesothelioma.

over 2 years ago

IO biomarker

ALK (Anaplastic lymphoma kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2) • HMGB1 (High Mobility Group Box 1)

CDKN2A deletion • NF2 negative

Ibrance (palbociclib) • APG-2449

over2years

Case Report of Selumetinib as a Novel Therapy in an NF2-Associated Ependymoma (AAN 2022)

Defective Merlin protein leads to overactivation of the Mitogen-activated protein kinase (MEK) pathway and parallel mammalian target of rapamycin (mTOR) pathway.Limited targeted therapy exists for NF2 associated tumors but includes everolimus (mTOR inhibitor). Although the tumor lacked somatic NF2 mutation, SMARCB1 mutations can occur in isolation. SMARCB1 mutated tumors are associated with overactivation of the MEK pathway, which may explain tumor response to selumetinib. This case highlights the potential for targeted therapies in NF2-associated tumors.

over 2 years ago

Clinical

SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)

NF2 mutation • SMARCB1 mutation • NF2 negative

everolimus • Koselugo (selumetinib)

almost4years

A Rapid Robust Method for Subgrouping Non-NF2 Meningiomas According to Genotype and Detection of Lower Levels of M2 Macrophages in AKT1 E17K Mutated Tumours. (PubMed, Int J Mol Sci)

Our data suggested that underlying tumour genetics play a part in the development of the immune composition of the tumour microenvironment. Stratifying meningiomas by mutational status and correlating this with their cellular composition will aid in the development of new immunotherapies for patients.

almost 4 years ago

Journal

AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CD163 (CD163 Molecule)

AKT1 E17K • NF2 mutation • NF2 negative

4years

YAP1-FAM118B Fusion Defines a Rare Subset of Childhood and Young Adulthood Meningiomas. (PubMed, Am J Surg Pathol)

DNA methylation profiling further distinguished YAP1-fusion meningiomas from those observed in ependymomas. In summary, we expand the genetic spectrum of somatic alteration associated with NF2 wild-type meningioma to include the YAP1-FAM118B fusion and provide support for aberrant signaling pathways potentially targetable by therapeutic intervention.

4 years ago

Clinical • Journal

EGFR (Epidermal growth factor receptor) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • YAP1 (Yes associated protein 1)

EGFR overexpression • MET overexpression • NF2 negative