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CANCER:

Malignant Pleural Mesothelioma

Related cancers:
1d
A Study of Nivolumab and Chemotherapy Followed by Surgery for Mesothelioma (clinicaltrials.gov)
P1, N=22, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=35 --> 22
Enrollment closed • Enrollment change
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Opdivo (nivolumab) • cisplatin • carboplatin • pemetrexed
1d
The BAP1 nuclear deubiquitinase is involved in the nonhomologous end-joining pathway of double-strand DNA repair through interaction with DNA-PK. (PubMed, Oncogene)
Combination treatment with X-ray irradiation and gemcitabine (as a radiosensitizer) strongly suppressed the growth of BAP1-deficient cells. Our results suggest reciprocal positive interactions between BAP1 and DNA-PKcs, based on phosphorylation of BAP1 by the latter and deubiquitination of DNA-PKcs by BAP1. Thus, functional interaction of BAP1 with DNA-PKcs supports a role for BAP1 in NHEJ DNA repair and may provide the basis for new therapeutic strategies and new insights into its role as a tumor suppressor.
Journal • BRCA Biomarker
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BAP1 (BRCA1 Associated Protein 1) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit)
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gemcitabine
2d
Study of Cadonilimab Combined With Bevacizumab and Standard Chemotherapy as First Line Therapy in Unresectable Pleural Mesothelioma (clinicaltrials.gov)
P2, N=38, Recruiting, Sun Yat-sen University | Initiation date: Jul 2023 --> Nov 2023 | Not yet recruiting --> Recruiting
Enrollment open • Trial initiation date • Combination therapy
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Avastin (bevacizumab) • carboplatin • pemetrexed • Kaitanni (cadonilimab)
4d
ABILITY: A Beta-only IL-2 ImmunoTherapY Study (clinicaltrials.gov)
P1/2, N=115, Recruiting, Medicenna Therapeutics, Inc. | Trial primary completion date: Sep 2024 --> Jun 2026
Trial primary completion date • Combination therapy • Checkpoint inhibition • Metastases
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Keytruda (pembrolizumab) • MDNA11
6d
EORTC-SPECTA Arcagen study, comprehensive genomic profiling and treatment adaptation of rare thoracic cancers. (PubMed, NPJ Precis Oncol)
MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.
Journal • Tumor mutational burden • MSi-H Biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)
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MSI-H/dMMR
7d
A Phase II Clinical Trial to Evaluate Safety and Efficacy of XmAb20717 in Advanced Rare Cancers (clinicaltrials.gov)
P2, N=140, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025
Trial completion date • Trial primary completion date • Metastases
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MSI (Microsatellite instability)
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MSI-H/dMMR
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vudalimab (XmAb717)
7d
Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas (clinicaltrials.gov)
P1, N=240, Recruiting, Inhibrx, Inc. | Trial completion date: Dec 2024 --> Jul 2026 | Trial primary completion date: Aug 2024 --> Dec 2025
Trial completion date • Trial primary completion date • Metastases
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cisplatin • carboplatin • 5-fluorouracil • temozolomide • pemetrexed • irinotecan • INBRX-109
17d
Mesothelioma of the tunica vaginalis testis. (PubMed, Ugeskr Laeger)
Fluorescence in situ hybridization, DNA and RNA next-generation sequencing showed no mesothelioma-associated tumour suppressor gene mutations, but deletion of CDKN2A and a rare TFG-ADGRG7 fusion both reported in pleural mesotheliomas, were detected. Clinicians should consider malignancy in case of discrepancy between symptoms and objective findings in scrotal conditions.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ADGRG7 (Adhesion G Protein-Coupled Receptor G7)
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CDKN2A deletion
18d
Immunotherapy for non-small cell lung cancer. (PubMed, Respir Investig)
However, treatment efficacy varies greatly from case to case, and no biomarkers have been developed to accurately predict efficacy. In this article, we discuss the past and future of ICI therapy for lung cancer, based on clinical and basic evidence accumulated to-date.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4)
22d
BAP1, Wilms' tumor 1, and calretinin in predicting survival and response to first-line chemotherapy in patients with pleural mesothelioma. (PubMed, J Cancer Res Clin Oncol)
The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.
Journal
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BAP1 (BRCA1 Associated Protein 1) • WT1 (WT1 Transcription Factor)
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pemetrexed
22d
SCITH-MESO: Molecular, Pathologic Intra Tumoral Heterogeneity in Malignant Pleural Mesothelioma (clinicaltrials.gov)
P=N/A, N=30, Recruiting, Hospices Civils de Lyon | Not yet recruiting --> Recruiting
Enrollment open
25d
Specific Targeting of Mesothelin-Expressing Malignant Cells Using Nanobody-Functionalized Magneto-Fluorescent Nanoassemblies. (PubMed, Int J Nanomedicine)
A 3D cell culture model based on MSLN-expressing multicellular tumor spheroids reveals NA penetration in the first superficial layers. Altogether, these results open the path to novel anticancer strategies based on MSLN-activated internalization of NA incorporating drugs to promote specific accumulation of active treatments in tumors.
Journal
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MSLN (Mesothelin) • DNM3 (Dynamin 3)
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MSLN expression
28d
Transarterial Chemoperfusion: Cisplatin, Methotrexate, Gemcitabine for Unresectable Pleural Mesothelioma (clinicaltrials.gov)
P2, N=34, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2023 --> Dec 2024
Trial completion date
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cisplatin • gemcitabine • methotrexate
1m
Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma. (PubMed, Diagn Cytopathol)
It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.
Journal • Cytology
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1)
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CDKN2A deletion
1m
SAKK 17/18 (ORIGIN) MPM & NSCLC >1st Line Gemci & Atezo Ph II (clinicaltrials.gov)
P2, N=68, Active, not recruiting, Swiss Group for Clinical Cancer Research | Trial completion date: Sep 2024 --> May 2024 | Trial primary completion date: Sep 2024 --> May 2024
Trial completion date • Trial primary completion date • Checkpoint inhibition • Metastases
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CD4 (CD4 Molecule)
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Tecentriq (atezolizumab) • gemcitabine
1m
Neoadjuvant Durvalumab and Tremelimumab With and Without Chemotherapy for Mesothelioma (clinicaltrials.gov)
P1/2, N=52, Not yet recruiting, Baylor College of Medicine | Initiation date: Sep 2023 --> Jan 2024
Trial initiation date
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cisplatin • carboplatin • Imfinzi (durvalumab) • Imjudo (tremelimumab) • pemetrexed
1m
Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (clinicaltrials.gov)
P2/3, N=520, Active, not recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2023 --> Jun 2024
Trial completion date • Metastases
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Keytruda (pembrolizumab) • cisplatin • pemetrexed
1m
NX-1607-101: A Study of NX-1607 in Adults With Advanced Malignancies (clinicaltrials.gov)
P1, N=345, Recruiting, Nurix Therapeutics, Inc. | Phase classification: P1b --> P1 | Trial completion date: Feb 2025 --> Feb 2026
Phase classification • Trial completion date • Metastases
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paclitaxel • oxaliplatin • irinotecan • NX-1607
1m
Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma. (PubMed, Cancers (Basel))
Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.
Journal
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CRP (C-reactive protein)
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Low PLR
2ms
Enrollment change • Trial completion date
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PD-L1 expression
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Keytruda (pembrolizumab) • pegenzileukin (SAR444245)
2ms
Comparison of immunohistochemistry, next generation sequencing and fluorescence in situ hybridization for detection of MTAP loss in pleural mesothelioma. (PubMed, Mod Pathol)
We show that MTAP IHC and molecular assays are complementary in detecting 9p21 homozygous deletion. MTAP IHC may be particularly useful for low tumor purity samples and in low-resource settings.
Journal • Next-generation sequencing
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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CDKN2A deletion • MTAP deletion
2ms
APG-2449 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=150, Recruiting, Ascentage Pharma Group Inc.
Trial completion date • Trial primary completion date • Metastases
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ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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ALK positive • ROS1 fusion • ROS1 positive • ALK-ROS1 fusion
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APG-2449
2ms
The combination of soluble forms of PD-1 and PD-L1 as a predictive marker of PD-1 blockade in patients with advanced cancers: a multicenter retrospective study. (PubMed, Front Immunol)
We retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13-2.83], p = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99-2.91], p = 0.05) compared with all other patients. Our findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.
Retrospective data • Journal • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
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MSI-H/dMMR
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Keytruda (pembrolizumab) • Opdivo (nivolumab)
2ms
Phase I Evaluation of Immunotoxin LMB-100 Administered by Normothermic, Intrapleural Perfusion Following Cytoreductive Surgery in Participants With Pleural Mesotheliomas, or Pleural Effusions From Cancers Expressing Mesothelin (clinicaltrials.gov)
P1, N=42, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2024 | Trial primary completion date: Dec 2026 --> Dec 2024
Trial completion date • Trial primary completion date • Surgery
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MSLN (Mesothelin)
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MSLN expression • MSLN positive
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LMB-100
2ms
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma (clinicaltrials.gov)
P2, N=30, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Phase classification: P1/2 --> P2
Phase classification • Checkpoint inhibition • Checkpoint block
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Opdivo (nivolumab) • Yervoy (ipilimumab)
2ms
The Current Treatment Landscape of Malignant Pleural Mesothelioma and Future Directions. (PubMed, Cancers (Basel))
So far, no single biomarker has been soundly correlated with targeted therapy development; thus, combination strategies are often required to improve outcomes. Locally applied vaccines, the expansion of genetically engineered immune cell populations such as T cells, the blockage of immune checkpoints that inhibit anti-tumorigenic responses and chemoimmunotherapy are among the most promising options expected to change the mesothelioma treatment landscape.
Review • Journal • Tumor mutational burden • IO biomarker
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TMB (Tumor Mutational Burden)
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TMB-L
2ms
Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy. (PubMed, Cancers (Basel))
The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA...The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.
Review • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden)
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PD-L1 expression
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Opdivo (nivolumab) • Avastin (bevacizumab) • Yervoy (ipilimumab)
2ms
Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers. (PubMed, Transl Oncol)
Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.
Journal
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MSLN (Mesothelin)
2ms
A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov)
P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=140 --> 6 | Trial primary completion date: Jun 2025 --> Nov 2023
Enrollment closed • Enrollment change • Trial primary completion date • Metastases
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MSLN (Mesothelin)
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MSLN expression • MSLN positive
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cyclophosphamide • fludarabine IV • TC-510
2ms
PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma. (PubMed, Front Oncol)
Multivariate analysis confirmed that PD-L1 expression was an independent factor for PFS and OS in patients with MPM and CALGB score of 5-6. PD-L1 addition to CALGB scale improves its prognostic estimation of MPM survival and should be considered in future research.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1)
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PD-L1 expression • PD-L1 overexpression • PD-L1-L
2ms
Niraparib plus Dostarlimab in Pleural Mesothelioma or Non-Small Cell Lung Cancer harboring HRR mutations: interim results of the UNITO-001 phase 2 prospective trial. (PubMed, Clin Cancer Res)
This preliminary analysis highlighted the lack of antitumor activity for the combination of niraparib and dostarlimab in patients with PM and/or advanced NSCLC harboring BAP1 somatic mutations. A potential antitumor activity emerged for PM with germline BAP1 and/or BRCA2 somatic mutations along with a good tolerability profile.
P2 data • Journal • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1)
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BRCA2 mutation • BAP1 mutation
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Zejula (niraparib) • Jemperli (dostarlimab-gxly)
2ms
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer (clinicaltrials.gov)
P1, N=74, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
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HER-2 negative
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cisplatin • gemcitabine • elimusertib (BAY 1895344)
2ms
Anti-PD1 does not improve pyroptosis induced by γδ T cells but promotes tumor regression in a pleural mesothelioma mouse model. (PubMed, Front Immunol)
However, we found no advantage for anti-PD-1 against PD-1 high expressing Vδ2 T cells in promoting pyroptosis. Taken together, our work demonstrated that Vδ2 T cells combined with anti-PD-1 antibody can be developed as a potential combination immunotherapy for mesothelioma.
Preclinical • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-L2 (Programmed Cell Death 1 Ligand 2) • IL2 (Interleukin 2) • CASP3 (Caspase 3) • IL18 (Interleukin 18) • BTN2A1 (Butyrophilin Subfamily 2 Member A1) • IL1B (Interleukin 1, beta) • BTN3A1 (Butyrophilin Subfamily 3 Member A1) • GSDME (Gasdermin E)
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PD-1 overexpression • PD-L2 expression
3ms
Validation of a Gene Expression Approach for the Cytological Diagnosis of Epithelioid and Biphasic Pleural Mesothelioma on a Consecutive Series. (PubMed, Cancers (Basel))
This tool can be complementary to ancillary markers, reducing invasive procedures and allowing an earlier diagnosis. Finally, the possibility to subtype PM on effusions strengthens the panel's role in PM diagnosis and management.
Journal
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • MSLN (Mesothelin)
3ms
Semaphorin 6 Family-An Important Yet Overlooked Group of Signaling Proteins Involved in Cancerogenesis. (PubMed, Cancers (Basel))
To date, very few studies have focused on the mechanisms of transmembrane SEMA6-driven tumor progression and its underlying interplay with RTKs within the tumor microenvironment. This review presents the growing evidence in the literature on the complex and shaping role of SEMA6 family proteins in cancer responsiveness to environmental stimuli.
Review • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor) • KDR (Kinase insert domain receptor)
3ms
Enrollment open
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Opdivo (nivolumab) • cisplatin • Yervoy (ipilimumab) • carboplatin • pemetrexed • volrustomig (MEDI5752)
3ms
LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study. (PubMed, BMC Cancer)
LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM.
Retrospective data • Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
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LAG3 (Lymphocyte Activating 3)
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LAG3 expression • LAG3 elevation
3ms
TRAcking Non-small Cell Lung Cancer Evolution Through Therapy (Rx) EVO (clinicaltrials.gov)
P=N/A, N=600, Recruiting, University College, London | Not yet recruiting --> Recruiting
Enrollment open
3ms
SWOG S0905: Pemetrexed Disodium and Cisplatin With or Without Cediranib Maleate in Treating Patients With Malignant Pleural Mesothelioma (clinicaltrials.gov)
P1/2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Phase classification: P2 --> P1/2
Phase classification • Combination therapy
|
cisplatin • pemetrexed • Recentin (cediranib)
3ms
Localized pleural mesothelioma in a dog. (PubMed, J Comp Pathol)
The animal was alive with no recurrence or metastasis/dissemination 11 months after surgery. To the best of our knowledge, this is the first report of a localized mesothelioma in a dog without metastasis/dissemination and highlights the value of mesothelial markers for an accurate diagnosis.
Journal
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NKX2-1 (NK2 Homeobox 1)
3ms
New P2 trial • Combination therapy
|
Keytruda (pembrolizumab) • cisplatin • carboplatin • pemetrexed
3ms
Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma. (PubMed, Diagn Pathol)
Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.
Journal • Cytology
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CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)
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CDKN2A deletion