Mesothelioma Research Articles

Exploring the role of pembrolizumab in mesothelioma: A single-arm analysis of available data.

e20097 Background: Malignant Mesothelioma (MMe) is a neoplasm of mesothelium and has a very poor survival rate. Over half the patients of MMe express programmed death-ligand 1 (PD-L1) which binds to the PD-1 receptor on T-cells which in turn suppresses their ability to kill tumors. Pembrolizumab is a PD-1 inhibitor antibody and it has shown efficacy in combating MMe. Our analysis aims to summarize data related to objective response rates (ORR) and adverse effects of Pembrolizumab therapy in MMe patients. Methods: We conducted an online search through PubMed, Cochrane, and Clinicaltrials.gov databases from their inception till January 25, 2024, to identify studies that reported the use of Pembrolizumab in patients with MMe. Data were extracted and analyzed and proportions with their 95% confidence interval have been reported. Onlinemeta v1.0 was used for all analyses. Results: A total of six studies with 549 patients reported the use of Pembrolizumab in patients with MMe. ORR was observed in 36.2% (32.3% - 40.4%; p < 0.01) of patients receiving Pembrolizumab while 20.4% (17.2%- 24.0%; p < 0.01) of patients experienced adverse effects of the therapy. Median survival ranged from 9.5 to 17.3 months whereas progression-free survival ranged from 2.5 to 7.1 months in patients. Conclusions: Pembrolizumab has an ORR and safety profile comparable to other immunotherapies. Further studies are needed to extensively study the drug and its effects in detail in patients with MMe. [Table: see text]

Disease monitoring using plasma-based circulating tumor DNA (ctDNA) assays in rare malignancies.

e15046 Background: ctDNA assays can be used to assess molecular residual disease, and the value of ctDNA monitoring in disease surveillance and treatment response assessment has been demonstrated in colon, breast, lung, and bladder cancers. However, the data of ctDNA in rare cancers has been lacking. We conducted this retrospective study to investigate the potential roles of ctDNA monitoring in rare tumors in both surveillance and response evaluation. Methods: ctDNA assay results of 12 patients (pts) with rare cancers including adrenocortical carcinoma (ACC) (4 pts), salivary gland cancers (3 pts), pleural or peritoneal malignant mesothelioma (4 pts), and anaplastic thyroid cancer (ATC) (1pt) undergoing treatment or surveillance in 2023 at Mayo Clinic Florida were analyzed. The trends of ctDNA levels were correlated with radiographic images findings. Results: Among the 12 patients, ctDNA was detected in at least one time point in 9 (75%) pts, including 1 (100%) ATC pt, 2 (66%) salivary gland pts, 3 (75%) malignant mesothelioma pts, and 3 (75%) ACC pts. Among these 9 pts, 5 pts had ctDNA collected at more than one timepoints, and the trends of ctDNA levels were consistent with image findings in all 5 pts. Among these 5 pts, one pt received definitive surgery for ACC with clearance of ctDNA after the surgery and one salivary gland cancer pt was undergoing surveillance and later developed disease progression. The other 3 pts were undergoing palliative systemic therapy and had responded to treatments. Conclusions: ctDNA was detectable in majority of the patients with rare malignancies reviewed in this study, including ACC, ATC, pleural or peritoneal malignant mesothelioma, and salivary gland cancers. Further study is warranted to investigate the role of ctDNA monitoring in surveillance and treatment response evaluation in rare malignancies.

Immune checkpoint inhibitors in advanced malignant peritoneal mesothelioma: Clinical insights, immunopathologic profiling, and prognostic implications from a single-center study.

e14665 Background: Malignant peritoneal mesothelioma (MPM) is a rare malignancy of the peritoneum. In patients with advanced disease, therapeutic options are limited, and prognosis is usually poor. While the role of immune-checkpoint inhibitors (ICI) in MPM is evolving, clinical data is scarce and there are currently no biomarkers to predict response to ICI therapy in this population. Methods: Patients treated at the Sheba Medical Center between 2016-2022 have been examined with the aim of delineating the clinical and immunopathologic characteristics of MPM, including programmed-death ligand-1 (PDL-1) status. Results: Forty-two patients with MPM were treated at Sheba during the study period. Eight patients (19%) have received immunotherapy as a single treatment in our cohort, all as ≥2 line of treatment. Of these patients, 3 patients (37.5%) had complete response (CR) or partial response (PR) as their best response, 3 patients (37.5%) had stable disease (SD), and 2 patients (25%) had progressive disease. Median overall survival (OS) among responding patients (CR/PR) and patients with clinical benefit (CR/PR/SD) were 6.8 years and 5.2 years, respectively, noticeably higher than the median OS for MPM (2.5 years). PDL-1 status was available for 23 patients: 17/23 (74%) had negative PDL-1 status and 6/23 (26%) had positive PDL-1 status. No correlation was observed in PDL-1 status among patients experiencing clinical benefit from treatment with ICIs. Conclusions: ICI therapy could be considered as a reasonable option for second-line therapy and beyond for MPM, with selected patients who may substantially benefit from these treatments. PDL-1 status did not correlate with treatment benefit, which highlights the limitation of this biomarker as a predictor of response in MPM patients.

Prognostic impact of clinical stage on non-surgical patients with pleural mesothelioma.

e20096 Background: Most patients with pleural mesothelioma (PM) are not surgical candidates and receive systemic therapy. Clinical stage is usually not reported in mesothelioma clinical trials. We evaluated the prognostic impact of clinical stage in mesothelioma using a large database with the hypothesis that M1 patients will have worse OS compared to M0 patients. Methods: The Surveillance, Epidemiology and End Results (SEER) Program was used to identify adult patients with PM diagnosed between 2004 and 2020, who received chemotherapy and did not undergo surgery. Patients with unknown stage were excluded. Staging was subdivided into I, II-III and IV for better accuracy. Age, sex, and stage were included in multivariable analyses (MVAs) using a Cox proportional hazard regression model. Unadjusted OS was estimated by the Kaplan-Meier method and compared using log-rank tests. Results: Among the 10,422 patients, 2,644 (25.4%) met the inclusion criteria. Histology classification was not available for 1,120 patients (42.4%), which were reported as malignant mesothelioma. Most patients were male (78.3%) and older than 70 years (54.5%). There were 970 patients (36.7%) with stage I, 893 (33.8%) with stage II-III and 781 (29.5%) with stage IV. The median OS for all patients was 11 months, with 1-year, 3-year and 5-year OS of 43.9%, 10.3% and 4.3% respectively. The median OS for stages I, II-III, and IV was 13 months, 11 months, and 9 months respectively, with 1-year OS of 50.5%, 42.8% and 36.9% respectively and 5-year OS for stages I, II-III, and IV of 5.3%, 3.0% and 4.9% respectively. The median and 1-year OS were 12 months and 46.8% respectively for M0 and 9 months and 36.9% respectively for M1 (p < 0.001). For patient with M0, the median OS for N0, N1 and N2 was 12 months, 11 months, and 11 months, respectively. In MVA, worse OS was observed in patients with age 71 or older compared to < 60 (HR 1.24, 1.09-1.4), and in male patients compared to females (HR 1.27, 1.15.-1.4). Stage IV was associated with worse OS when compared to stage II-III (HR 1.11, 1.001-1.23, p = 0.04) and stage I (HR 1.34, 1.21-1.49, p < 0.001) while stage II-III was associated with worse OS compared to stage I (HR 1.21, 1.1-1.33, p = 0.0001). Conclusions: Clinical stage is a significant predictor for outcomes in patients with unresected pleural mesothelioma treated with chemotherapy, has been underreported, and should be included in clinical trials for a better evaluation of novel treatment strategies.

Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis.

e14683 Background: Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies. Methods: We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed. In our study, patients with grade 1 or grade 2 CIPs were defined as low-grade CIPs, and patients with grade 3, grade 4 or grade 5 CIPs were defined as high-grade CIPs. Results: The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31-78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. Most of the patients were diagnosed with lung cancer (36 patients, 85.7%). There were 3 patients with esophageal squamous cell cancer, 1 patient with hepatic cell cancer, 1 patient with gastric signet ring cell cancer and 1 patient with pericardial malignant mesothelioma. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs. Conclusions: The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

Sarcomatoid malignant pleural mesothelioma: a case of long-term recurrence-free survival following curative intent surgery alone

BackgroundCurative intent surgery may be indicated for some patients with resectable early stage malignant pleural mesothelioma (MPM). However, sarcomatoid MPM is a highly aggressive subtype for which curative intent surgery is generally not recommended.Case presentationWe present the case of a 63-year-old man who presented with dyspnea and chest tightness. Computed tomography revealed pleural thickening and nodular lesions. A pleural biopsy confirmed lymphohistiocytoid MPM (cT1N0M0, stage IA), prompting surgical intervention. The patient underwent left extrapleural pneumonectomy (EPP), and the final diagnosis was sarcomatoid MPM (pT2N0M0, stage IB). Although post-operative chemotherapy was planned, the patient refused additional treatment, because of the introduction of home oxygen therapy, and has remained recurrence-free for 10 years after the surgery.ConclusionsThis case presents a noteworthy instance of achieving long-term recurrence-free survival solely through curative intent surgery for sarcomatoid MPM. It highlights the potential efficacy of surgical intervention in managing this aggressive subtype, offering a glimmer of hope for improved outcomes. Further research is warranted to better define the role of surgery in the treatment of sarcomatoid MPM.

FK228 suppress the growth of human malignant pleural mesothelioma tumor independent to epithelioid or non-epithelioid histology

Human malignant pleural mesothelioma (hMPM) is an aggressive, rare disease with a poor prognosis. Histologically, MPM is categorized into epithelioid, biphasic, and sarcomatoid subtypes, with the epithelioid subtype generally displaying a better response to treatment. Conversely, effective therapies for the non-epithelioid subtypes are limited. This study aimed to investigate the potential role of FK228, a histone deacetylase inhibitor, in the suppression of hMPM tumor growth. We conducted a comprehensive analysis of the histological and molecular characteristics of two MPM cell lines, CRL-5820 (epithelioid) and CRL-5946 (non-epithelioid). CRL-5946 cells and non-epithelioid patient-derived xenografted mice exhibited heightened growth rates compared to those with epithelioid MPM. Both CRL-5946 cells and non-epithelioid mice displayed a poor response to cisplatin. However, FK228 markedly inhibited the growth of both epithelioid and non-epithelioid tumor cells in vitro and in vivo. Cell cycle analysis revealed FK228-induced G1/S and mitotic arrest in MPM cells. Caspase inhibitor experiments demonstrated that FK228-triggered apoptosis occurred via a caspase-dependent pathway in CRL-5946 but not in CRL-5820 cells. Additionally, a cytokine array analysis showed that FK228 reduced the release of growth factors, including platelet-derived and vascular endothelial growth factors, specifically in CRL-5946 cells. These results indicate that FK228 exhibits therapeutic potential in MPM by inducing cytotoxicity and modulating the tumor microenvironment, potentially benefiting both epithelioid and non-epithelioid subtypes.

Comprehensive analysis to identify PUS7 as a prognostic biomarker from pan-cancer analysis to osteosarcoma validation.

Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine synthases, but the literature on this enzyme is limited to several cancer types. Currently, no investigation has been performed on the systematic pan-cancer analysis concerning PUS7 role in cancer diagnosis and prognosis. Employing public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), UALCAN and Tumor Immune Single-cell Hub (TISCH), this work investigated the PUS7 carcinogenesis in pan-cancer. Differential expression analysis, prognostic survival analysis and biological function were systematically performed. Furthermore, PUS7 potential as an osteosarcoma biomarker for diagnosis and prognosis was assessed in this study. The findings indicated that PUS7 was overexpressed in the majority of malignancies. High PUS7 expression contributed to the poor prognosis among 11 cancer types, including Adrenocortical Cancer (ACC), Bladder Cancer (BLCA), Liver Cancer (LIHC), Kidney Papillary Cell Carcinoma (KIRP), Mesothelioma (MESO), Lower Grade Glioma (LGG), Kidney Chromophobe (KICH), Sarcoma (SARC), osteosarcoma (OS), Pancreatic Cancer (PAAD), and Thyroid Cancer (THCA). In addition, elevated PUS7 expression was linked to advanced TNM across multiple malignancies, including ACC, BLCA, KIRP, LIHC and PAAD. The function enrichment analysis revealed that PUS7 participates in E2F targets, G2M checkpoint, ribosome biogenesis, and rRNA metabolic process. Moreover, PUS7 is also a reliable biomarker and a potential therapeutic target for osteosarcoma. In summary, PUS7 is a putative pan-cancer biomarker that reliably forecasts cancer patients' prognosis. In addition, this enzyme regulates the cell cycle, ribosome biogenesis, and rRNA metabolism. Most importantly, PUS7 possibly regulates osteosarcoma initiation and progression.

VISTA‐targeted antibody‐drug conjugates exhibit potent antitumor effects on malignant pleural mesothelioma

AbstractMalignant pleural mesothelioma (MPM) is a malignant tumor of the pulmonary pleural tissue for which there is a lack of effective targeted therapy. In this study, moderate to high V‐domain immunoglobulin T‐cell activation suppressor (VISTA) expression levels were observed in most MPM clinical tumor samples. We prepared two high‐affinity anti‐VISTA monoclonal antibodies (mAbs) and generated two novel VISTA‐targeted antibody‐drug conjugates (ADCs) by conjugating anti‐VISTA mAbs with the potent cytotoxic drug monomethyl auristatin E (MMAE). αV1‐MMAE and αV2‐MMAE showed potent killing effects to VISTA‐positive cell lines in vitro, with half‐maximal inhibitory concentration (IC50) of nanomolar levels. αV1‐MMAE and αV2‐MMAE were also able to significantly induce apoptosis and cause G2/M phase arrest in VISTA‐positive cells. In the VISTA‐positive human MPM xenograft model, both αV1‐MMAE and αV2‐MMAE showed significant antitumor activity, led to a significant survival advantage compared to mice in the control group, and effectively induced apoptosis in the tumor tissues of mice. In conclusion, we demonstrated that the novel VISTA‐targeted ADCs (αV1‐MMAE and αV2‐MMAE), especially αV1‐MMAE, had potent killing effects against VISTA‐positive MPM cells both in vitro and in vivo. Therefore, through further development, they may have the potential to become new drugs for the treatment of MPM.

Analysis of Treatment Strategies and Outcomes in Malignant Peritoneal Mesothelioma: Insights From a Multi-Center Study

BackgroundThis study aimed to evaluate the demographic,” clinicopathologic, and prognostic characteristics of malignant peritoneal mesothelioma (MPeM), as well as the treatment options for the rare and heterogeneous MPeM population.MethodsA retrospective multi-center observational cohort study was conducted to evaluate patients with MPeM. Due to the heterogeneity of the study population, the study divided them into two main groups in terms of treatments, follow-up periods, and prognostic features. The first group comprised the patients who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and the second group included the patients with metastatic disease for whom curative intent surgery was not possible. The patients’ diagnostic procedures and treatments were identified from medical records. Patients older than 18 years old were included in the study regardless of asbestos exposure. Well-differentiated papillary and multicystic mesothelioma histologic types were not included in the study.ResultsThe study evaluated 118 patients from five centers. Survival times, prognosis, and treatment responses were analyzed in both groups. The study showed that CRS-HIPEC was associated with longer overall survival (OS) and progression-free survival (PFS). Perioperative therapy was evaluated in subgroup analyses of this population and shown to provide survival benefits. The patients treated with chemotherapy (metastatic and medically inoperable patients and those for whom complete cytoreduction was not achievable) had a poorer prognosis than the surgery group. The study showed that life expectancy decreased significantly for the patients not suitable to undergo surgery for any reason.ConclusionsAccording to data from experienced centers, CRS-HIPEC is a treatment option recognized as effective, cost-effective, and safe, with better OS and PFS , as well as low morbidity and mortality rates similar to those in the literature. In addition, the platinum-pemetrexed combination continues to be an effective and acceptable treatment option for metastatic patients, those who are medically inoperable, and those for whom complete or near-complete cytoreduction is not achievable.

Global burden of mesothelioma attributable to occupational asbestos exposure in 204 countries and territories: 1990–2019

Malignant mesothelioma, a rare and aggressive cancer primarily caused by occupational asbestos exposure, has a poor prognosis. This study leverages the Global Burden of Disease (GBD) 2019 dataset to analyze the burden of mesothelioma linked to occupational asbestos exposure from 1990 to 2019. The analysis includes the number of mesothelioma deaths and disability-adjusted life years (DALYs) attributable to occupational asbestos exposure, focusing on trends in age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) by year, age, sex, country, region, and Socio-demographic Index (SDI). In 2019, 91.7% of mesothelioma deaths and 85.2% of DALYs were attributable to occupational asbestos exposure, resulting in 26,820 (95% UI 24,312–28,622) deaths and 569,429 (95% UI 509,956–617,484) DALYs. Despite a decline in ASMR and ASDR from 1990 to 2019, the absolute number of deaths and DALYs almost doubled. The United States reported the highest number of mesothelioma deaths, while China had the highest number of DALYs. Age-specific mortality rates and DALYs decreased in the 25–74 age group but increased in the 75+ age group. In conclusion, occupational asbestos exposure remains the primary cause of mesothelioma worldwide, with an increasing number of deaths and DALYs. The highest incidence rates are observed in high-income areas, and rates are rising in low-income areas. It is crucial to raise awareness about the hazards of asbestos to reduce the global burden of mesothelioma linked to occupational exposure.

Genomic and T cell repertoire biomarkers associated with malignant mesothelioma survival.

Malignant mesothelioma (MM) is an exceedingly rare tumor with poor prognosis due to the limited availability of effective treatment. Immunotherapy has emerged as a novel treatment approach for MM, but less than 40% of the patients benefit from it. Thus, it is necessary to identify accurate and effective biomarkers that can predict the overall survival (OS) and immunotherapy efficacy for MM. DNA sequencing was used to identify the genomic landscape based on the data from 86 Chinese patients. T cell receptor (TCR) sequencing was used to characterize MM TCR repertoires of 28 patients between October 2016 and April 2023. Patients with TP53, NF2, or CDKN2A variants at the genomic level, as well as those exhibiting lower Shannon index (<6.637), lower evenness (<0.028), or higher clonality (≥0.194) according to baseline tumor tissue TCR indexes, demonstrated poorer OS. Furthermore, patients with TP53, CDKN2A, or CDKN2B variants and those with a lower evenness (<0.030) in baseline tumor tissue showed worse immunotherapy efficacy. The present study is the first to identify five special TCR Vβ-Jβ rearrangements associated with MM immunotherapy efficacy. The present study reported the largest-scale genomic landscape and TCR repertoire of MM in Chinese patients and identified genomic and TCR biomarkers for the prognosis and immunotherapy efficacy in MM. The study results might provide new insights for prospective MM trials using specific genes, TCR indexes, and TCR clones as biomarkers and offer a reference for future antitumor drugs based on TCR-specific clones.

Comprehensive Pulmonary Rehabilitation for Patients with Malignant Pleural Mesothelioma: A Feasibility Pilot Study.

Malignant pleural mesothelioma (MPM) represents a significant health burden, with limited treatment options and poor prognosis. Despite advances in pharmacological and surgical interventions, the role of rehabilitation in MPM management remains underexplored. This study aims to assess the feasibility of a tailored pulmonary rehabilitation intervention addressing physical and respiratory function in MPM patients. A prospective pilot study was conducted on surgically treated MPM patients referred to a cardiopulmonary rehabilitation service. The intervention comprised multidisciplinary educational sessions, physical rehabilitation, and respiratory physiotherapy. Feasibility was evaluated based on dropout rates, adherence to the rehabilitation program, safety, and patient-reported outcomes. Twelve patients were initially enrolled, with seven completing the study. High adherence to physical (T1: 93.43%, T2: 82.56%) and respiratory (T1: 96.2%, T2: 92.5%) rehabilitation was observed, with minimal adverse events reported. Patient satisfaction remained high throughout the study (GPE scores at T1: 1.83 ± 1.17; T2: 2.0 ± 1.15), with improvements noted in physical function, pain management, and health-related quality of life. However, some issues, such as time constraints and lack of continuous supervision, were reported by participants. This pilot study demonstrates the feasibility and potential benefits of a tailored pulmonary rehabilitation intervention in MPM patients. Despite its promising outcomes, further research with larger samples is warranted to validate its efficacy and integrate rehabilitation as a component into the multidisciplinary management of MPM.

Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions

BackgroundMalignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of ~2.5 years.MethodsWe constructed the protein interactome of 59 MPeM-associated genes with previously known protein-protein interactions (PPIs) as well as novel PPIs predicted using our previously developed HiPPIP computational model and analysed it for transcriptomic and functional associations and for repurposable drugs.ResultsThe MPeM interactome had over 400 computationally predicted PPIs and 4700 known PPIs. Transcriptomic evidence validated 75.6% of the genes in the interactome and 65% of the novel interactors. Some genes had tissue-specific expression in extramedullary hematopoietic sites and the expression of some genes could be correlated with unfavourable prognoses in various cancers. 39 out of 152 drugs that target the proteins in the interactome were identified as potentially repurposable for MPeM, with 29 having evidence from prior clinical trials, animal models or cell lines for effectiveness against peritoneal and pleural mesothelioma and primary peritoneal cancer. Functional modules related to chromosomal segregation, transcriptional dysregulation, IL-6 production and hematopoiesis were identified from the interactome. The MPeM interactome overlapped significantly with the malignant pleural mesothelioma interactome, revealing shared molecular pathways.ConclusionsOur findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results.

Targeting inflammatory factors for chemoprevention and cancer interception to tackle malignant mesothelioma.

Mesothelioma is an incurable cancer of the mesothelial lining often caused by exposure to asbestos. Asbestos-induced inflammation is a significant contributing factor in the development of mesothelioma, and genetic factors also play a role in the susceptibility to this rapidly progressive and treatment-resistant malignancy. Consequently, novel approaches are urgently needed to treat mesothelioma and prevent or reduce the overall incidence of this fatal disease. In this research perspective, we review the current state of chemoprevention and cancer interception progress in asbestos-induced mesothelioma. We discuss the different preclinical mouse models used for these investigations and the inflammatory factors that may be potential targets for mesothelioma prevention. Preliminary studies with naturally occurring phytochemicals and synthetic agents are reviewed. Results of previous clinical chemoprevention trials in populations exposed to asbestos and considerations regarding future trials are also presented.

Targeted Therapy in Mesotheliomas: Uphill All the Way.

Mesothelioma (MM) is an aggressive and lethal disease with few therapeutic opportunities. Platinum-pemetrexed chemotherapy is the backbone of first-line treatment for MM. The introduction of immunotherapy (IO) has been the only novelty of the last decades, allowing an increase in survival compared to standard chemotherapy (CT). However, IO is not approved for epithelioid histology in many countries. Therefore, therapy for relapsed MM remains an unmet clinical need, and the prognosis of MM remains poor, with an average survival of only 18 months. Increasing evidence reveals MM complexity and heterogeneity, of which histological classification fails to explain. Thus, scientific focus on possibly new molecular markers or cellular targets is increasing, together with the search for target therapies directed towards them. The molecular landscape of MM is characterized by inactivating tumor suppressor alterations, the most common of which is found in CDKN2A, BAP1, MTAP, and NF2. In addition, cellular targets such as mesothelin or metabolic enzymes such as ASS1 could be potentially amenable to specific therapies. This review examines the major targets and relative attempts of therapeutic approaches to provide an overview of the potential prospects for treating this rare neoplasm.

Advances in Targeted Therapy for Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare cancer with high malignancy and aggressiveness on the pleural, caused by the following risk factors including asbestos inhalation, genetic factors, and genetic mutation. The present chemotherapy, antiangiogenic therapy, and immunotherapy methods are ineffective and the survival time of patients is very short. There is an urgent need to find potential therapeutic targets for MPM. At present, it has been found the following types of targets: gene mutation targets such as BRCA associated protein 1 (BAP1) and cyclin-dependent kinase 2A (CDKN2A); epigenetic targets such as lysine (K)-specific demethylase 4A (KDM4A) and lysine-specific demethylase 1 (LSD1), and signal protein targets such as glucose-regulated protein 78 (GRP78) and signal transducer and activator of transcription 3 (STAT3). So far, available clinical trials include phase II clinical trials of histone methyltransferase inhibitor Tazemetostat, poly (ADP-ribose) polymerase (PARP) inhibitor Rucaparib and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib, as well as phase I clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy (CAR-T) cell injection in the thoracic cavity and TEA domain family member (TEAD) inhibitor VT3989 and IK-930, and the results of these trials have showed certain clinical efficacy. .

Epithelial Cell Adhesion Molecule (EpCAM) Expression in Human Tumors: A Comparison with Pan-Cytokeratin and TROP2 in 14,832 Tumors.

EpCAM is expressed in many epithelial tumors and is used for the distinction of malignant mesotheliomas from adenocarcinomas and as a surrogate pan-epithelial marker. A tissue microarray containing 14,832 samples from 120 different tumor categories was analyzed by immunohistochemistry. EpCAM staining was compared with TROP2 and CKpan. EpCAM staining was detectable in 99 tumor categories. Among 78 epithelial tumor types, the EpCAM positivity rate was ≥90% in 60 categories-including adenocarcinomas, neuroendocrine neoplasms, and germ cell tumors. EpCAM staining was the lowest in hepatocellular carcinomas, adrenocortical tumors, renal cell neoplasms, and in poorly differentiated carcinomas. A comparison of EpCAM and CKpan staining identified a high concordance but EpCAM was higher in testicular seminomas and neuroendocrine neoplasms and CKpan in hepatocellular carcinomas, mesotheliomas, and poorly differentiated non-neuroendocrine tumors. A comparison of EpCAM and TROP2 revealed a higher rate of TROP2 positivity in squamous cell carcinomas and lower rates in many gastrointestinal adenocarcinomas, testicular germ cell tumors, neuroendocrine neoplasms, and renal cell tumors. These data confirm EpCAM as a surrogate epithelial marker for adenocarcinomas and its diagnostic utility for the distinction of malignant mesotheliomas. In comparison to CKpan and TROP2 antibodies, EpCAM staining is particularly common in seminomas and in neuroendocrine neoplasms.

Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study

ObjectivesRecruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or...

Two Cases with Rapidly Developing Malignant Pericardial Mesothelioma

Two Cases with Rapidly Developing Malignant Pericardial Mesothelioma