News - MET overexpression

10d

ADVL1622: Cabozantinib-S-Malate in Treating Younger Patients With Recurrent, Refractory, or Newly Diagnosed Sarcomas, Wilms Tumor, or Other Rare Tumors (clinicaltrials.gov)

P2, N=109, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Sep 2024

10 days ago

Trial completion date

MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • AXL (AXL Receptor Tyrosine Kinase)

MET amplification • MET overexpression • RET mutation • MET mutation • RET rearrangement • AXL overexpression

Cabometyx (cabozantinib tablet) • Cometriq (cabozantinib capsule)

16d

Progress of antibody-drug conjugates (ADCs) targeting c-Met in cancer therapy; insights from clinical and preclinical studies. (PubMed, Drug Deliv Transl Res)

Of great note, there are currently nine c-Met-targeting ADCs being examined in different phases of clinical studies as well as eight preclinical studies for treating various solid tumors. The purpose of this study is to present a broad overview of clinical- and preclinical-stage c-Met-targeting ADCs.

16 days ago

Preclinical • Review • Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET overexpression

HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors. (PubMed, Transl Lung Cancer Res)

Combination treatment with lorlatinib and erlotinib significantly reduced HRG1-induced activation of RTK signaling in ALK-positive NSCLC cells. HER3 overexpression has potential as a prognostic marker in ALK-positive NSCLCs, including ALK-TKI naïve and treated cases, especially those with EML4-ALK V1/V2. Assessing HER3 expression may be crucial for treatment planning and outcome prediction in these patients.

1 month ago

Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • EML4 (EMAP Like 4) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)

HER-2 expression • ALK positive • EGFR overexpression • MET overexpression • EML4-ALK fusion • ALK fusion • ERBB3 expression • MET expression • ERBB3 overexpression • EML4-ALK fusion + ALK positive • EML4-ALK variant 1

erlotinib • Lorbrena (lorlatinib)

Prediction of MET Overexpression in Lung Adenocarcinoma from Hematoxylin and Eosin Images. (PubMed, Am J Pathol)

This model was evaluated on an independent holdout test set of 300 over-expressed and 289 normal patients, demonstrating an ROC-AUC of 0.70 (95th percentile interval: 0.66 - 0.74) with stable performance characteristics across different patient clinical variables and robust to synthetic noise on the test set. These results suggest that H&E-based predictive models could be useful to prioritize patients for confirmatory testing of MET protein or MET gene expression status.

1 month ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET overexpression • MET expression

Anlotinib Inhibits Cisplatin Resistance in Non-Small-Cell Lung Cancer Cells by Inhibiting MCL-1 Expression via MET/STAT3/Akt Pathway. (PubMed, Can Respir J)

Anlotinib is an effective targeted therapy for advanced non-small-cell lung cancer (NSCLC) and has been found to mediate chemoresistance in many cancers. Furthermore, MET overexpression reversed the inhibitory effect of anlotinib on the DDP resistance of NSCLC cells, and this effect could be eliminated by MCL-1 knockdown or ACT001 (an inhibitor for STAT3/Akt pathway). Our results confirmed that anlotinib inhibited DDP resistance in NSCLC cells, which might decrease MCL-1 expression via mediating the MET/STAT3/Akt pathway.

1 month ago

Journal

MCL1 (Myeloid cell leukemia 1)

MET overexpression • MET expression • MCL1 expression • STAT3 expression

cisplatin • Focus V (anlotinib) • dimethylamino micheliolide (ACT001)

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.

1 month ago

Preclinical • Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • TWIST1 (Twist Family BHLH Transcription Factor 1)

MET amplification • MET overexpression • MET mutation • CDKN1B expression

TeliMET NSCLC-01: A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)

P3; Trial completion date: Jul 2026 --> Mar 2028

1 month ago

Trial completion date • Adverse events • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • MET overexpression

CONFIRM anti-Total c-MET (SP44) Rabbit Monoclonal Primary Antibody

docetaxel • telisotuzumab vedotin (ABBV-399)

Rational Design of PARP1/c-Met Dual Inhibitors for Overcoming PARP1 Inhibitor Resistance Induced by c-Met Overexpression. (PubMed, J Med Chem)

Importantly, compound 16 demonstrates superior antitumor potency compared to the PARP1 inhibitor Olaparib and the c-Met inhibitor Crizotinib, either alone or in combination, in MDA-MB-231 and HCT116OR xenograft models. These findings highlight the potential of PARP1/c-Met dual inhibitors for expanding the indications of PARP1 inhibitors and overcoming tumor cells' resistance to them.

1 month ago

Journal • PARP Biomarker

MET (MET proto-oncogene, receptor tyrosine kinase)

MET overexpression

Lynparza (olaparib) • Xalkori (crizotinib)

2ms

Deubiquitinase BRCC3 promotes the migration, invasion and EMT progression of colon adenocarcinoma by stabilizing MET expression. (PubMed, Genes Genomics)

BRCC3 acted as a critical factor in the development of COAD by deubiquitinating and stabilizing MET, which might provide an emerging biomarker for the therapeutic and diagnosis strategy of COAD.

2 months ago

Journal • BRCA Biomarker

MET (MET proto-oncogene, receptor tyrosine kinase)

MET overexpression • MET expression

2ms

P3; Trial completion date: Mar 2028 --> Jul 2026

2 months ago

Trial completion date • Adverse events • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • MET overexpression

CONFIRM anti-Total c-MET (SP44) Rabbit Monoclonal Primary Antibody

docetaxel • telisotuzumab vedotin (ABBV-399)

2ms

SOUND: Savolitinib Combine With Durvalumab in EGFR Wild-type Locally Advanced or Metastatic NSCLC (clinicaltrials.gov)

P2, N=60, Suspended, AstraZeneca | Recruiting --> Suspended

2 months ago

Trial suspension • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • EGFR wild-type • MET exon 14 mutation • MET overexpression • MET mutation

Imfinzi (durvalumab) • Orpathys (savolitinib)

2ms

MET overexpression correlated with prognosis of EGFR-mutant treatment‑naïve advanced lung adenocarcinoma: a real‑world retrospective study. (PubMed, Clin Transl Oncol)

MET positive expression was an independent predictor of poor outcomes in untreated EGFR L858R mutation advanced LUAD patients treated with first-line EGFR-TKI monotherapy.

2 months ago

Retrospective data • Journal • Real-world evidence • Real-world • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR expression • MET overexpression • EGFR L861Q • EGFR S768I • MET expression • MET positive • EGFR G719A • EGFR G719C

2ms

Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Adult Patients With Mesenchymal Epithelial Transition Factor (MET) Overexpressing Advanced Cancer (clinicaltrials.gov)

P1/2, N=237, Recruiting, Regeneron Pharmaceuticals | N=83 --> 237 | Trial completion date: Dec 2026 --> Feb 2030 | Trial primary completion date: Dec 2026 --> Feb 2030

2 months ago

Enrollment change • Trial completion date • Trial primary completion date • Metastases

MET overexpression

Libtayo (cemiplimab-rwlc) • REGN5093-M114

2ms

AcSé: Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1 (clinicaltrials.gov)

P2, N=246, Completed, UNICANCER | Active, not recruiting --> Completed

2 months ago

Trial completion

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ALK positive • MET overexpression • ALK translocation

Xalkori (crizotinib)

2ms

To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of ABN401 in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer Harboring c-MET Dysregulation (clinicaltrials.gov)

P1, N=78, Recruiting, Abion Inc | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

2 months ago

Trial completion date • Trial primary completion date • Metastases

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET overexpression

babamekip (ABN401)

2ms

Activity of Tepotinib in Hepatocellular Carcinoma With High-Level MET Amplification: Preclinical and Clinical Evidence. (PubMed, JCO Precis Oncol)

High-level METamp may be an oncogenic driver in HCC that is sensitive to MET inhibitors such as tepotinib.

2 months ago

Preclinical • Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET overexpression

Tepmetko (tepotinib)

2ms

Unraveling the Significance of MET Focal Amplification in Lung Cancer: Integrative NGS, FISH, and IHC Investigation. (PubMed, Mod Pathol)

Notably, a strong correlation was observed between focal amplification and PD-L1 expression, indicating potential therapeutic implications with combined MET inhibitor and immunotherapy for patients with both alterations. Our findings provide insights into the molecular complexity and clinical relevance of METamp in lung cancer, highlighting the role of MET focal amplification as an oncogenic driver and its feasibility as a primary biomarker to further investigate the clinical activity of MET inhibitors in future studies.

2 months ago

Journal • Next-generation sequencing • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)

PD-L1 expression • MET amplification • MET overexpression • MET expression • PD-L1 amplification

2ms

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.

2 months ago

Preclinical • Journal

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)

BRAF mutation • NRAS mutation • MET overexpression • GNAQ mutation • MET mutation • GNAQ Q209L • HGF expression

3ms

FLOWERS: Osimertinib With or Without Savolitinib as 1L in de Novo MET+, EGFR+ NSCLC (clinicaltrials.gov)

P2, N=44, Active, not recruiting, Guangdong Association of Clinical Trials | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed

MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • MET amplification • MET overexpression • MET expression

Tagrisso (osimertinib) • Orpathys (savolitinib)

3ms

KIF20B and MET, hub genes of DIAPHs, predict poor prognosis and promote pancreatic cancer progression. (PubMed, Pathol Res Pract)

DIAPHs, KIF20B, and MET are promising candidates for the prognosis and treatment of PC. More importantly, downregulation of KIF20B and MET inhibited pancreatic cancer progression by regulating LDHA and EMT.

3 months ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • LDHA (Lactate dehydrogenase A) • CD8 (cluster of differentiation 8) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD73 (5'-Nucleotidase Ecto) • CD44 (CD44 Molecule) • NT5E (5'-Nucleotidase Ecto) • DIAPH3 (Diaphanous Related Formin 3)

MET overexpression • MET expression

3ms

miR-200a involvement in the biological behavior of hepatoma carcinoma cells by targeting the regulatory expression of mesenchymal-epithelial transition factor (PubMed, Zhonghua Gan Zang Bing Za Zhi)

The control group and co-transfection group were between the two groups, and the difference between the groups was statistically significant (P <0.05). HepG2 cell proliferation, migration, invasion, and cell apoptosis induction can be inhibited by miR-200a, and the functional mechanism for this may be associated with the miR-200a target's ability to down-regulate MET expression in HepG2 cells.

3 months ago

Journal • IO biomarker

MET (MET proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • CASP3 (Caspase 3) • MIR200A (MicroRNA 200a) • ANXA5 (Annexin A5)

MET overexpression • MET expression • BCL2 expression • MIF overexpression • BAX expression

3ms

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer. (PubMed, Breast Cancer Res)

Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

3 months ago

Journal • Circulating tumor cells • Tumor cell • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • EPCAM (Epithelial cell adhesion molecule)

HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • MET overexpression • ER mutation • MET expression • ESR1 mutation • MET positive • HR positive + HER-2 negative • PTEN mutation + HR positive

3ms

MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature. (PubMed, Ther Adv Med Oncol)

Moreover, our review provides an overview of and recommendations on the selection of various cross-platform technologies for the detection of MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion. Furthermore, challenges and hurdles underlying these common detection platforms are discussed.

3 months ago

Review • Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET overexpression • MET fusion

4ms

Chinese expert consensus on clinical practice of MET detection in non-small cell lung cancer. (PubMed, Ther Adv Med Oncol)

Since there are many types of MET alterations and related testing methods, as well as many problems and challenges during clinical testing, further sorting and standardization are required. Combined with clinical practice experience, literature review, and expert discussion, the writing group developed this consensus on the three main types of MET alterations (METex14 skipping, MET gene amplification, and MET protein overexpression) in order to guide the practical applications of clinical MET testing.

4 months ago

Review • Journal

EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)

MET amplification • MET exon 14 mutation • MET overexpression • MET fusion

4ms

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.

4 months ago

P1 data • Journal

EGFR (Epidermal growth factor receptor) • AXL (AXL Receptor Tyrosine Kinase)

EGFR mutation • MET amplification • MET overexpression • MET mutation • AXL expression • AXL overexpression

gefitinib • ningetinib (CT053PTSA)

4ms

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov)

P2, N=360, Recruiting, AstraZeneca | Trial primary completion date: May 2024 --> Aug 2024

4 months ago

Trial primary completion date • Combination therapy • Metastases

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

EGFR mutation • EGFR L858R • EGFR exon 19 deletion • MET amplification • EGFR amplification • MET overexpression • MET mutation

Tagrisso (osimertinib) • Orpathys (savolitinib)

4ms

Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib. (PubMed, Ther Adv Med Oncol)

The most common adverse reactions (ARs) due to savolitinib administration are nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. This consensus was developed through two rounds of extensive national surveys involving multidisciplinary experts in China, aiming to guide clinicians to prevent and treat various ARs scientifically, and improve the efficacy of the drug and the quality of life of patients.

4 months ago

Journal • Adverse drug reaction

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET overexpression

Orpathys (savolitinib)

5ms

AcSé: Phase 2 Study Assessing Efficacy and Safety of Crizotinib in Patients Harboring an Alteration on ALK, MET or ROS1 (clinicaltrials.gov)

P2, N=246, Active, not recruiting, UNICANCER | Trial completion date: Jan 2023 --> Jan 2024

5 months ago

Trial completion date

ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

ALK positive • MET overexpression • ALK translocation

Xalkori (crizotinib)

5ms

A phase 2, open-label study of amivantamab in patients with previously treated advanced or metastatic gastric or esophageal cancer. (ASCO-GI 2024)

Ami showed clinical meaningful antitumor activity in EC, especially in Met-high-expression tumors. There was minimal monotherapy activity in GC. No new safety signals were identified in pts with GC and EC, which appeared to be acceptable.

5 months ago

Clinical • P2 data • Metastases

EGFR (Epidermal growth factor receptor)

EGFR expression • MET overexpression • MET expression

Rybrevant (amivantamab-vmjw)

5ms

A novel combination therapy with Cabozantinib and Honokiol effectively inhibits c-Met-Nrf2-induced renal tumor growth through increased oxidative stress. (PubMed, Redox Biol)

In a tumor xenograft model, this combination treatment markedly inhibited renal tumor growth in vivo; and it is associated with decreased expression of Rubicon, p62, HO-1 and vessel density in the tumor tissues. Together, cabozantinib + Honokiol combination can significantly inhibit c-Met-induced and Nrf2-mediated anti-oxidant pathway in renal cancer cells to promote increased oxidative stress and tumor cell death.

5 months ago

Journal • Combination therapy

MET (MET proto-oncogene, receptor tyrosine kinase) • HMOX1 (Heme Oxygenase 1)

MET overexpression

Cabometyx (cabozantinib tablet)

5ms

MET overexpression in ovarian cancer via CD24-induced downregulation of miR-181a: A signalling for cellular quiescence-like state and chemoresistance in ovarian CSCs. (PubMed, Cell Prolif)

And, CD24 or MET knockdown or miR-181a overexpression inhibited the manifestation of CSC phenotypes, cellular quiescence-like state and chemoresistance, in OV90 and SK-OV-3 cells: increased colony formation, decreased G0/G1 phase cell population and increased sensitivity to Cisplatin and Carboplatin. Our findings suggest that CD24-miR-181a-MET may consist of a signalling route for ovarian CSCs, therefore being a combinatory set of markers and therapeutic targets for ovarian CSCs.

5 months ago

Journal

CD24 (CD24 Molecule) • MIR181A1 (MicroRNA 181a-1) • YY1 (YY1 Transcription Factor)

MET overexpression • MET expression • CD24 overexpression • CD24 expression

cisplatin • carboplatin

5ms

Histo-Molecular Factors of Response to Combined Chemotherapy and Immunotherapy in Non-Small Cell Lung Cancers. (PubMed, Target Oncol)

This study suggests that the efficacy of combining pembrolizumab with pemetrexed and platinum-based chemotherapy differs according to the histo-molecular biomarkers, which may help to identify patients liable to benefit from CIT.

5 months ago

Clinical • Journal • PD(L)-1 Biomarker • IO biomarker

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) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11)

TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • HER-2 amplification • MET amplification • ALK rearrangement • MET exon 14 mutation • STK11 mutation • MET overexpression • RET mutation • MET mutation • RET rearrangement

Keytruda (pembrolizumab) • pemetrexed

5ms

METRIX: A Study to Assess Prevalence of a Specific Protein Overexpression in Adult Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov)

P=N/A, N=500, Recruiting, AbbVie | Not yet recruiting --> Recruiting

5 months ago

Enrollment open • Real-world evidence • Real-world

MET overexpression

6ms

P1, N=78, Recruiting, Abion Inc | Phase classification: P1/2 --> P1

6 months ago

Phase classification • Metastases

MET (MET proto-oncogene, receptor tyrosine kinase)

MET amplification • MET exon 14 mutation • MET overexpression

babamekip (ABN401)

6ms

Feasibility and utility of the novel cancer comprehensive genomic profiling RNA-seq for the identification of therapeutic targets and diagnostic biomarkers in glioma (SNO 2023)

TOP RNA panel detects more fusions than DNA panel and is utilized not only for the detection of molecular targets but also for the molecular classification of glioma, providing treatments optimized for the individual patients.

6 months ago

CDK4 (Cyclin-dependent kinase 4)

MET overexpression • IDH wild-type • MET fusion

Todai OncoPanel (TOP)

6ms

Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR. (PubMed, J Exp Clin Cancer Res)

Our findings highlight the potential of DOXA as a therapeutic option for metastatic TNBC, warranting further investigation.

6 months ago

Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD24 (CD24 Molecule) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1)

EGFR overexpression • MET overexpression

6ms

c-Met immunohistochemistry as reflex test at diagnosis for non-small cell lung cancer: a real-world experience from a monocentric case series. (PubMed, J Clin Pathol)

Systematic c-Met testing in daily routine for NSCLC patients is feasible, highlighting a potential correlation with clinicopathological and molecular features.

6 months ago

Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Reflex

PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase)

PD-L1 expression • PD-L1 overexpression • MET overexpression • MET expression • MET positive

6ms

Receptor tyrosine kinase gene expression profiling of orbital rhabdomyosarcoma unveils MET as a potential biomarker and therapeutic target. (PubMed, Hum Cell)

Well-separated tumor clusters confirmed the association between MET gene and collective expression of RTK genes. Therefore, the therapeutic potential of multi-kinase inhibitors targeting MET and the 9 other significant RTKs needs to be explored.

6 months ago

Journal

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • FLT1 (Fms-related tyrosine kinase 1) • FLT4 (Fms-related tyrosine kinase 4) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • FCGR2A (Fc fragment of IgG receptor IIa) • PDGFA (Platelet Derived Growth Factor Subunit A) • PDGFB (Platelet Derived Growth Factor Subunit B) • FCGR2B (Fc Fragment Of IgG Receptor IIb)

MET overexpression • MET expression • AXL overexpression • FGFR1 expression • FLT1 expression • RET expression

6ms

Evaluating the role of CDK4/6 inhibition on STAT3 activation in a transgenic mouse model of HER2-positive breast cancer (SABCS 2023)

We demonstrate STAT3 activation in a mouse model of HER2 driven breast cancer and show persistent activation in recurrent tumors lacking HER2 expression rendering them resistant to HER2-targeted therapy. We also demonstrate the anti-tumor effect of palbociclib in primary tumors with HER2-dependent proliferation. Taken together, our findings suggest that pSTAT3 is a viable therapeutic target and provides the rationale for combination therapy with CDK4/6 inhibition using palbociclib and STAT3 inhibition with a novel STAT3 inhibitor in HER2-positive breast cancer.

6 months ago

Preclinical

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCND1 (Cyclin D1) • STAT3 (Signal Transducer And Activator Of Transcription 3)

HER-2 positive • HR positive • HER-2 overexpression • HER-2 expression • MET overexpression • CCND1 overexpression • ER expression • STAT3 overexpression

Ibrance (palbociclib)

6ms

pH-Responsive and Actively Targeted Metal-Organic Framework Structures for Multimodal Antitumor Therapy and Inhibition of Tumor Invasion and Metastasis. (PubMed, ACS Appl Mater Interfaces)

In this study, our team designed a pH-sensitive nanoparticle CAB/Ce6@ZIF-8@PEG-FA (CCZP) loaded with CAB and Ce6, which exerted a multimodal therapeutic effect of PDT and molecularly targeted therapy by laser irradiation, and the PDT-induced overexpression of MET and VEGFR could also be inhibited by the target of CAB, thus reducing the invasive tumor cells metastasis. In summary, CCZP gives full play to the advantages of both drugs, exerting multimodal treatment while reducing HCC invasion and metastasis, providing a safe, potential approach to clinical treatment.

6 months ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase)

MET overexpression • MET overexpression + KDR overexpression

Cabometyx (cabozantinib tablet)

6ms

Characterization of MET Overexpression (OE) and Impact on Prognosis in a Real-world, Single-Site Cohort of Patients With Nonsquamous Non-small Cell Lung Cancer (NSq NSCLC) (AMP 2023)

Introduction: Telisotuzumab vedotin (Teliso-V) is a first-in-class antibodydrug conjugate that delivers a cytotoxic payload directly to tumor cells with MET protein (or c-Met) OE... MET OE was detected in 25% of samples, most of which were negative for METamp and MET mutations. A subpopulation of METamp patients did not have MET OE. NSCLC with MET OE was associated with worse prognosis compared with NSCLC with no MET OE in the context of standard-of-care treatment.

6 months ago

Real-world evidence • Clinical • PD(L)-1 Biomarker • IO biomarker • Real-world

EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)

PD-L1 expression • MET amplification • EGFR wild-type • MET exon 14 mutation • MET overexpression • MET mutation • MET expression

PD-L1 IHC 22C3 pharmDx

telisotuzumab vedotin (ABBV-399)