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BIOMARKER:

MET mutation

i
Other names: DFNB97, AUTS9, RCCP2, C-Met, HGFR, HGF Receptor, Met Proto-Oncogene, HGF/SF Receptor, Proto-Oncogene C-Met, Scatter Factor Receptor, Tyrosine-Protein Kinase Met, Hepatocyte Growth Factor Receptor, MET, MET Proto-Oncogene, Receptor Tyrosine Kinase
Entrez ID:
1d
CHRYSALIS: Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=751, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Jun 2025
Trial completion date • Metastases
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ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR exon 20 insertion • EGFR wild-type • MET exon 14 mutation • EGFR C797S • MET mutation • MET expression • EGFR exon 20 mutation • EGFR positive
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carboplatin • pemetrexed • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
7d
Genetically driven predisposition leads to an unusually genomic unstable renal cell carcinoma. (PubMed, Discov Oncol)
While BRCA1 and RAD51 germline mutations are well-characterised in breast and ovarian cancer, their role in renal cell carcinoma is still largely unexplored. The genomic instability detected in this case of renal cell carcinoma, along with the presence of unusual mutations, might offer support to clinicians for the development of patient-tailored therapies.
Journal • Tumor mutational burden • BRCA Biomarker
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TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • VHL (von Hippel-Lindau tumor suppressor) • RAD51 (RAD51 Homolog A) • FH (Fumarate Hydratase) • FLCN (Folliculin)
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BRCA1 mutation • TMB-H • VHL mutation • MET mutation • FLCN mutation • RAD51 mutation
13d
TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer. (PubMed, Oncogene)
TWIST1 mediated MET TKI resistance through suppression of p27 expression and genetic or pharmacologic inhibition of TWIST1 overcame TKI resistance in vitro and in vivo. Our findings suggest that targeting TWIST1 may be an effective therapeutic strategy to overcome resistance in MET-driven NSCLC as well as in other oncogene driven subtypes in which MET amplification is the resistance mechanism.
Preclinical • Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • TWIST1 (Twist Family BHLH Transcription Factor 1)
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MET amplification • MET overexpression • MET mutation • CDKN1B expression
13d
Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients With Advanced or Refractory Solid Tumours (clinicaltrials.gov)
P1, N=25, Recruiting, DeuterOncology | N=15 --> 25 | Trial completion date: Nov 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Oct 2024
Enrollment change • Trial completion date • Trial primary completion date • Metastases
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MET mutation
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DO-2
15d
Bevacizumab improved prognosis for advanced EGFR-mutant lung adenocarcinoma with brain metastasis receiving cerebral radiotherapy. (PubMed, Clin Transl Oncol)
In patients with BM from EGFR-mutated NSCLC, cerebral radiotherapy with bevacizumab markedly improved OS. This improvement was more evident after cerebral radiotherapy.
Journal • Metastases
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • MET mutation
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Avastin (bevacizumab)
16d
The Prevalence and Radiologic Features of Renal Cancers Associated with FLCN, BAP1, SDH, and MET Germline Mutations. (PubMed, Radiol Imaging Cancer)
Within the study sample size limits, imaging findings for hereditary RCC overlapped with those of nonhereditary RCC, and the prevalence of other associated benign solid renal lesions (other than complex cysts) was up to 11%. Keywords: Familial Renal Cell Carcinoma, Birt-Hogg-Dubé Syndrome, Carcinoma, Renal Cell, Paragangliomas, Urinary, Kidney
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase) • BAP1 (BRCA1 Associated Protein 1) • FLCN (Folliculin)
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BAP1 mutation • MET mutation • FLCN mutation
17d
Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns. (PubMed, Cell Commun Signal)
These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.
Journal • Metastases
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ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein) • MEN1 (Menin 1)
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MET mutation
21d
Molecular features and clinical outcomes of EGFR-mutated, MET-amplified non-small-cell lung cancer after resistance to dual-targeted therapy. (PubMed, Ther Adv Med Oncol)
This study revealed a heterogeneous landscape of resistance mechanisms to EGFR/MET DTT, with a similar prevalence of on- and off-target mechanisms. Targeted therapy or CT, as compared to BSC, exhibited the potential to improve survival outcomes for patients with advanced NSCLC following resistance to DTT.
Clinical data • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • MET mutation
23d
First NGS-based companion diagnostic to aid in selecting non-small cell lung cancer patients with ERBB2 (HER2) activating mutations for treatment with trastuzumab deruxtecan (AACR 2024)
The 6 AV studies met the necessary product requirements and acceptance criteria to detect clinical samples with ERBB2 mutations. Additionally, the CV study clinical accuracy and clinical efficacy results demonstrated the safety and effectiveness of the use of the ODxTT in FFPE samples as an aid to identify NSCLC patients eligible for treatment with the Daiichi Sankyo lung cancer therapeutic T-DXd.
Clinical • Next-generation sequencing • Companion diagnostic
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation • MET mutation
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Oncomine™ Dx Target Test • TruSight Tumor 170 Assay
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Enhertu (fam-trastuzumab deruxtecan-nxki)
23d
Real-world data analysis of comprehensive genomic profiling using plasma samples from non-small cell lung cancer patients (AACR 2024)
In patients without known driver oncogenes, mutations associated with approved therapeutic implications were detected in 12.0%. The detection of gene rearrangements using liquid biopsy may be limited compared with genetic mutations.
Clinical • Real-world evidence • Real-world
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • RET fusion • ALK rearrangement • MET exon 14 mutation • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • KRAS G12
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FoundationOne® Liquid CDx
25d
DCLRE1B/Apollo germline mutations associated with renal cell carcinoma impair telomere protection. (PubMed, Biochim Biophys Acta Mol Basis Dis)
Our results strongly suggest that ApolloN246I and ApolloY273H are loss-of-function mutants that cause impaired telomere integrity and could lead to genomic instability. Altogether, our results suggest that mutations in Apollo could induce renal oncogenesis.
Journal
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FLCN (Folliculin) • TERF2 (Telomeric Repeat Binding Factor 2)
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VHL mutation • MET mutation
26d
Trial suspension • Metastases
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • EGFR wild-type • MET exon 14 mutation • MET overexpression • MET mutation
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Imfinzi (durvalumab) • Orpathys (savolitinib)
28d
Efficacy of immunotherapy in patients with oncogene-driven non-small-cell lung cancer: a systematic review and meta-analysis. (PubMed, Ther Adv Med Oncol)
EGFR-, ALK-, HER2-, RET-, and ROS1-altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. KRAS G12C mutation, BRAF non-V600E mutation, and MET amplification have better responses to immunotherapy, and more prospective studies are needed for further research.
Retrospective data • Review • Journal • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • MET amplification • MET exon 14 mutation • MET mutation • KRAS G12
30d
PD-L1 expression and its correlation with clinicopathological and molecular characteristics in Chinese patients with non-small cell lung cancer. (PubMed, Medicine (Baltimore))
In our study, PD-L1 expression was significantly higher in squamous cell carcinomas and lower in adenocarcinomas, and was positively associated with MET and KRAS mutations, as well as the wild-type EGFR gene state. Nonetheless, additional studies are needed to further validate those associations and determine the clinical significance for immune checkpoint inhibitors of these factors.
Journal • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
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PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • PD-L1 overexpression • BRAF V600 • EGFR wild-type • MET exon 14 mutation • PD-L1 negative • MET mutation • ALK translocation
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PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
1m
Study to Evaluate Safety and PK of CHS-006 in Combination With Toripalimab in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=22, Active, not recruiting, Coherus Biosciences, Inc. | Recruiting --> Active, not recruiting | N=100 --> 22
Enrollment closed • Enrollment change • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • ALK mutation • MET mutation • ROS1 mutation
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Loqtorzi (toripalimab-tpzi) • CHS-006
1m
Investigating Hereditary Risk In Thoracic Cancers (INHERIT) (clinicaltrials.gov)
P=N/A, N=500, Recruiting, Dana-Farber Cancer Institute | Active, not recruiting --> Recruiting
Enrollment open
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • YAP1 (Yes associated protein 1)
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EGFR mutation • EGFR T790M • MET mutation • EGFR R776H
1m
Prognostic Significance of Circulating Tumour Cells (CTCs) and Circulating Tumour DNA (ctDNA) in High-Grade Serous Ovarian Cancer (USCAP 2024)
We report that with the use of CTCID markers, single and clusters CTCs can be isolated from ovarian cancer patients with prognostic significance. CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.
Circulating tumor cells • BRCA Biomarker • Circulating tumor DNA • Tumor cell
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • MUC16 (Mucin 16, Cell Surface Associated) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • EPCAM (Epithelial cell adhesion molecule)
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TP53 mutation • KRAS mutation • BRCA1 mutation • MET mutation
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Parsortix Liquid Biopsy
1m
Cytomorphology of Non-Small Cell Lung Carcinoma with MET Exon 14 Skipping Mutations (USCAP 2024)
One patient received Capmatinib and one patient Pembrolizumab. This study showed that NSCLC with METex14 are poorly differenciated tumors with necrotic background,multinucleation,atypical mitoses,and pleomorphic/sarcomatoid features. Larger studies are needed to confirm our preliminary findings. Routine NGS testing on cytological specimens is feasible and essential for METex14 testing and select patients with advanced lung NSCLC for targeted therapies.
PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • NKX2-1 (NK2 Homeobox 1)
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TP53 mutation • HER-2 amplification • HER-2 mutation • MET amplification • MET exon 14 mutation • MET mutation • TP53 amplification
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Oncomine Focus Assay
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Keytruda (pembrolizumab) • Tabrecta (capmatinib)
1m
Fumarate-Deficient Uterine Leiomyosarcoma: Molecular Confirmation of Four Cases (USCAP 2024)
While exceedingly rarely, FH mutations may be found in uLMS. Confirmation of FH deficiency should not preclude the diagnosis of sarcoma in smooth muscle neoplasms that meet histologic criteria for malignancy.
Clinical
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TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • FH (Fumarate Hydratase)
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TP53 mutation • MET mutation • RB1 deletion • ATRX mutation • RB deletion
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FoundationOne® Heme CDx
1m
Non-Small Cell Lung Carcinomas with MET Exon 2 Skipping Mutations: A Potential Inhibitory Self-Regulatory Mechanism by Tumor Cells (USCAP 2024)
MET-exon-2 skipping was documented as a potential self-regulating mechanism of tumor cells by decreasing abundance of Met mRNA encoding a functional Met receptor. Our findings suggest that advanced stage non-small cell lung carcinomas may trigger one such regulatory event to balance cancerous growth of tumor against coexisting pathogenic mutations especially of genes from the MAPK pathways. These observations are novel and may help shed light on mechanisms that regulate tumor growth, facilitate biomarker development for prognostics, and help design therapeutic targets.
Tumor cell
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • STK11 (Serine/threonine kinase 11) • MLH1 (MutL homolog 1)
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TP53 mutation • KRAS mutation • BRAF mutation • MET exon 14 mutation • MET mutation
|
FusionPlex® Pan Solid Tumor v2 panel
1m
The Efficacy and Safety of Treating Acquired MET Resistance Through Combinations of Parent and MET Tyrosine Kinase Inhibitors in Patients With Metastatic Oncogene-Driven NSCLC. (PubMed, JTO Clin Res Rep)
Multi-institutional retrospective chart review identified 83 patients with metastatic oncogene-driven NSCLC that were separated into the following two pairwise matched cohorts: (1) MET cohort (n = 41)-patients with acquired MET resistance continuing their parent TKI with a MET TKI added or (2) Chemotherapy cohort (n = 42)-patients without any actionable resistance continuing their parent TKI with a platinum-pemetrexed added...The efficacy and safety of combining MET TKIs (crizotinib, capmatinib, or tepotinib) with parent TKIs for acquired MET resistance are efficacious. Radiographic response and AEs did not differ significantly on the basis of the underlying MET TKI used. Loss of MET gene amplification, development of MET on-target mutations, Ras-Raf-MAPK alterations, and EGFR gene amplification were molecular patterns found on progression with dual parent and MET TKI combinations.
Journal • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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TP53 mutation • EGFR mutation • MET amplification • EGFR amplification • MET exon 14 mutation • RAS mutation • MET mutation • MET fusion
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Xalkori (crizotinib) • pemetrexed • Tepmetko (tepotinib) • Tabrecta (capmatinib)
1m
Transactivation of Met signaling by oncogenic Gnaq drives the evolution of melanoma in Hgf-Cdk4 mice. (PubMed, Cancer Gene Ther)
Overexpression of oncogenic GnaqQ209L in the immortalized melanocyte cell line promoted in vivo growth that was enhanced by transgenic Hgf expression in the tumor microenvironment. This cross-signaling mechanism explains the selection of oncogenic Gnaq/11 in primary Hgf-Cdk4 melanomas and provides an example of how oncogenic driver mutations, intracellular signaling cascades, and microenvironmental cues cooperate to drive cancer development in a tissue-specific fashion.
Preclinical • Journal
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • GNAQ (G Protein Subunit Alpha Q) • CDK4 (Cyclin-dependent kinase 4) • HGF (Hepatocyte growth factor)
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BRAF mutation • NRAS mutation • MET overexpression • GNAQ mutation • MET mutation • GNAQ Q209L • HGF expression
1m
Comparison of Tepotinib, Paclitaxel, or Ramucirumab Efficacy According to the Copy Number or Phosphorylation Status of the MET Gene: Doublet Treatment versus Single Agent Treatment. (PubMed, Int J Mol Sci)
These in vitro findings suggest that compared with ramucirumab-plus-paclitaxel, tepotinib-plus-paclitaxel better inhibits the growth of c-MET-positive GC cells, cells lacking MET amplification but containing phosphorylated MET, and cells containing MET mutations. Clinical studies are required to confirm the therapeutic effects of these regimens.
Journal
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation • MET positive
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paclitaxel • Cyramza (ramucirumab) • Tepmetko (tepotinib)
1m
Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer. (PubMed, Nat Med)
The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
Journal • Circulating tumor DNA • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
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HER-2 amplification • NTRK1 fusion • MET amplification • PTEN mutation • RAS wild-type • MET mutation • HER-2 amplification + MET amplification
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Avastin (bevacizumab) • Vectibix (panitumumab) • oxaliplatin
2ms
Feasibility of detecting NSCLC-associated fusion genes in long-term preserved FFPE samples (ELCC 2024)
The overall concordance rate was 93.3%, with concordance rates for each group are 97.7% (2-3 years), 100% (4 years), and 80.0% (≥ 5 years), respectively. Conclusions PCR effectively detects mRNA in long-term preserved FFPE samples, providing valuable variant information for treatment guidance in NSCLC patients, even after extended storage periods.
ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK positive • RET fusion • MET exon 14 mutation • ALK fusion • RET mutation • ROS1 fusion • MET mutation
|
AmoyDx® Pan Lung Cancer PCR Panel
2ms
Prevalence, clinical characteristics, and treatment outcomes of patients with KRAS-mutated non-squamous NSCLC and PD-L1 expression: Real-life data analysis (ELCC 2024)
Analysis of progression-free survival (PFS) after the first line of treatment with immune checkpoint inhibitors (ICIs) in 30 pts with stage IV KRAS-mutated NSCLC and high PD-L1 showed a trend favoring patients presenting a co-mutation (mPFS 13.7mo KRAS co-mutated vs. 3.6mo in KRAS only; HR 0.26; CI 95% 0.09-0.070; p=0.19). Conclusions These findings emphasize the importance of further exploring PD-L1 role in KRAS mutated patients, especially by taking into account accompanying mutations in other genes evaluated by NGS.
Clinical • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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PD-L1 expression • TP53 mutation • KRAS mutation • BRAF mutation • PIK3CA mutation • PTEN mutation • STK11 mutation • FGFR2 mutation • PD-L1 negative • KRAS wild-type • RAS wild-type • MET mutation • PIK3CA expression • KRAS expression
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VENTANA PD-L1 (SP263) Assay
2ms
Cytopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors in serous effusion (PubMed, Zhonghua Bing Li Xue Za Zhi)
This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.
Journal • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CD34 (CD34 molecule) • SALL4 (Spalt Like Transcription Factor 4) • SYP (Synaptophysin)
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TP53 mutation • HER-2 amplification • MET amplification • STK11 mutation • PD-L1 negative • CDKN2A mutation • MET mutation • BRCA2 deletion • SMARCA4 mutation • BRCA1 deletion
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PD-L1 IHC 22C3 pharmDx
2ms
Clinicopathological features of SMARCA4-deficient lung adenocarcinoma: a study of 42 cases (PubMed, Zhonghua Bing Li Xue Za Zhi)
It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.
Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1) • NAPSA (Napsin A Aspartic Peptidase)
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TP53 mutation • KRAS mutation • EGFR mutation • STK11 mutation • RET mutation • KEAP1 mutation • MET mutation • SMARCA4 mutation • NKX2-1 expression • TTF1 expression
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PD-L1 IHC 22C3 pharmDx
2ms
CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen (clinicaltrials.gov)
P2, N=219, Active, not recruiting, University of Campania "Luigi Vanvitelli" | Recruiting --> Active, not recruiting
Enrollment closed
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • RAS (Rat Sarcoma Virus)
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HER-2 amplification • HER-2 expression • MET amplification • BRAF wild-type • RAS mutation • MET mutation
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Erbitux (cetuximab) • 5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
2ms
Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib Resistant EGFR-Driven Lung Cancer. (PubMed, Cancer Res Commun)
Our results suggest osimertinib and savolitinib combination is most effective for osimertinib resistant EGFR-mutant tumors with MET pathway activation as evidenced by phospho-MET. As subclonal MET amplification may be evident in MET polysomy tumor progression, MET polysomy warrants close clinical follow up with phospho-MET IHC in parallel with FISH diagnostic.
Journal
|
EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET amplification • MET mutation • MET expression • EGFR mutation + MET-CEP7 fusion
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Tagrisso (osimertinib) • Orpathys (savolitinib)
2ms
Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling. (PubMed, Front Pharmacol)
Despite the improvement in response rates with various modulation strategies such as chemotherapy combined with targeted therapy, radiotherapy, and immunotherapy, the prognosis of mCRC is poor, with a 5-year survival rate of 14%, and the primary reason for treatment failure is believed to be the development of resistance to therapies. Herein, we provide an overview of the main mechanisms of resistance in mCRC and specifically highlight the role of drug transports, EGFR, and HGF/c-MET signaling pathway in mediating mCRC resistance, as well as discuss recent therapeutic approaches to reverse resistance caused by drug transports and resistance to anti-EGFR blockade caused by mutations in EGFR and alteration in HGF/c-MET signaling pathway.
Review • Journal • IO biomarker • Metastases
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • MET mutation
2ms
Efficacy, safety and genomic analysis of SCT200, an anti-EGFR monoclonal antibody, in patients with fluorouracil, irinotecan and oxaliplatin refractory RAS and BRAF wild-type metastatic colorectal cancer: a phase Ⅱ study. (PubMed, EBioMedicine)
SCT200 exhibited promising clinical efficacy and manageable safety profiles in RAS and BRAF wild-type mCRC patients progressed on fluorouracil, irinotecan and oxaliplatin treatment. The baseline ctDNA and ctDNA clearance status at the 7th week after the first dose of SCT200 administration before receiving SCT200 could be a potential prognostic biomarker for RAS and BRAF wild-type mCRC patients with SCT200 therapy.
Journal • Metastases
|
BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • RAS (Rat Sarcoma Virus)
|
MET amplification • BRAF wild-type • RAS mutation • MET mutation
|
5-fluorouracil • oxaliplatin • irinotecan • SCT200
3ms
Comprehensive Genomic Analysis of Patients With Non-Small-Cell Lung Cancer Using Blood-Based Circulating Tumor DNA Assay: Findings From the BFAST Database of a Single Center in Taiwan. (PubMed, JCO Precis Oncol)
NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results.
Journal • Circulating tumor DNA
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)
|
TP53 mutation • KRAS mutation • EGFR mutation • PIK3CA mutation • RET mutation • TET2 mutation • MET mutation
|
FoundationOne® Liquid CDx
3ms
Effectiveness and safety of amivantamab in EGFR exon 20 insertion (E20I) mutations in non-small cell lung cancer (NSCLC). (PubMed, Transl Lung Cancer Res)
The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor, which should be further validated.
Journal • PD(L)-1 Biomarker • IO biomarker • EGFR exon 20
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
|
PD-L1 expression • TP53 mutation • EGFR mutation • EGFR exon 20 insertion • MET mutation • EGFR exon 20 mutation
|
Rybrevant (amivantamab-vmjw)
3ms
Therapeutic strategy using novel RET/YES1 dual-target inhibitor in lung cancer. (PubMed, Biomed Pharmacother)
In this study, we investigated PLM-101, a novel dual-target inhibitor of RET/YES1, which exhibits notable anti-cancer activities against CCDC6-RET-positive cancer cells and anti-metastatic effects against YES1-positive cancer cells. Our findings shed light on the significance of the YES1-Cortactin-actin remodeling pathway in the metastasis of lung cancer cells, establishing YES1 as a promising target for suppression of metastasis. This paper unveils a novel inhibitor that effectively targets both RET and YES1, thereby demonstrating its potential to impede the growth and metastasis of RET rearrangement lung cancer.
Journal
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • CCDC6 (Coiled-Coil Domain Containing 6) • CTTN (Cortactin)
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EGFR mutation • ALK mutation • RET mutation • MET mutation • RET rearrangement • RET expression • RET positive
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Tagrisso (osimertinib) • dasatinib • PLD-101
3ms
Exploring the Clinical Utility of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic. (PubMed, J Am Coll Surg)
Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multi-center studies.
Journal • Tumor mutational burden • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
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BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • FGFR2 mutation • FGFR2 fusion • ROS1 fusion • MET mutation • FGFR3 amplification
3ms
Proffered Paper: Prognostic significance of circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA) in high-grade serous ovarian cancer (EACR-AACR 2024)
CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.
Circulating tumor cells • BRCA Biomarker • Circulating tumor DNA • Tumor cell
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • MUC16 (Mucin 16, Cell Surface Associated) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • EPCAM (Epithelial cell adhesion molecule)
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TP53 mutation • KRAS mutation • BRCA1 mutation • MET mutation
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Parsortix Liquid Biopsy
3ms
Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis. (PubMed, Lung Cancer)
This study demonstrates that combined blockade of MET, AXL and EGFR is a feasible strategy for a subset of EGFR-mutant NSCLC.
P1 data • Journal
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EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)
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EGFR mutation • MET amplification • MET overexpression • MET mutation • AXL expression • AXL overexpression
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gefitinib • ningetinib (CT053PTSA)
3ms
Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape. (PubMed, J Kidney Cancer VHL)
Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches.
Journal
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ARID1A (AT-rich interaction domain 1A) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C)
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MET mutation
3ms
Trial completion date • Trial primary completion date
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MET (MET proto-oncogene, receptor tyrosine kinase)
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MET amplification • MET exon 14 mutation • MET mutation
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MYTX-011
3ms
Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL). (PubMed, Genes (Basel))
New treatments on the horizon that attempt to maneuver around these resistance mutations can be met with new resistance mutations, creating an unmet need for patients with CLL. Novel therapies and combinations that address all forms of resistance are discussed.
Review • Journal
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BTK (Bruton Tyrosine Kinase)
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MET mutation • BTK mutation
3ms
A Retrospective Study: Evaluation of the Efficacy of Immunotherapy With Rare Mutations in Non-small Cell Lung Cancer (clinicaltrials.gov)
P=N/A, N=186, Recruiting, Yongchang Zhang | Trial completion date: Jan 2023 --> Jan 2025 | Trial primary completion date: Jan 2023 --> Jan 2024
Trial completion date • Trial primary completion date • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
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BRAF mutation • HER-2 mutation • ALK mutation • RET mutation • MET mutation