bims-mesote Biomed News
on Mesothelioma
Issue of 2024‒11‒17
nine papers selected by
Laura Mannarino, Humanitas Research



  1. Eur J Surg Oncol. 2024 Nov 07. pii: S0748-7983(24)01440-9. [Epub ahead of print]51(1): 109372
      BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes.METHODS: Data from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases.
    RESULTS: The study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9 % and 11.2 %, respectively, while for no-surgery patients, they were 34.9 % and 3.7 % (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95 % CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades.
    CONCLUSION: Surgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential.
    DOI:  https://doi.org/10.1016/j.ejso.2024.109372
  2. Gen Thorac Cardiovasc Surg Cases. 2023 Oct 03. 2(1): 57
      BACKGROUND: Pleural mesothelioma is an aggressive malignant tumor and has a poor prognosis. In particular, biphasic pleural mesothelioma is a less common histologic type, and successful outcomes are rare.CASE PRESENTATION: A 60-year-old man was referred to our associated hospital because of dyspnea. Massive right pleural effusion and thickening of the entire right parietal pleura were revealed by radiological examination. After pleural biopsy, we diagnosed the patient's tumor as biphasic pleural mesothelioma. The patient was admitted to our hospital for multimodal treatment. Two cycles of chemotherapy were initially administered with dramatic effects. Therefore, we decided to perform surgery and achieved a macroscopic complete resection. Postoperative chemotherapy was administered with no adverse events. No recurrence has been observed 11 months post-operation.
    CONCLUSIONS: We encountered a case of biphasic pleural mesothelioma that responded well to chemotherapy, enabling macroscopic complete resection.
    Keywords:  Biphasic pleural mesothelioma; Macroscopic complete resection; Multimodal therapy
    DOI:  https://doi.org/10.1186/s44215-023-00077-8
  3. Lung Cancer. 2024 Nov 07. pii: S0169-5002(24)00558-0. [Epub ahead of print]198 108024
      BACKGROUND: Previous studies showed opposite effects of NOTCH1 and NOTCH2 on mesothelioma cell survival under hypoxia. Mechanisms underlying these effects are not still clear and this pathway plays a key role in angiogenesis and cancer stem cells (CSCs) self-renewal processes.PURPOSE: In this study we evaluated whether NOTCH1, NOTCH2 copy number alterations (CNAs) might predict prognosis of patients with pleural mesothelioma (PM) and if the modulation of this pathway might target CSCs, potentiating pemetrexed activity, also in hypoxic conditions.
    METHODS: Recurrent CNAs were determined by high-resolution whole-genome sequencing from paraffin-embedded samples of a "discovery cohort" (26 patients treated with pemetrexed-based chemotherapy). Prognostic CNAs were validated by PCR gene copy-number and expression analyses in the "discovery" and in two independent "validation" cohorts of pemetrexed-treated and untreated patients (N = 45 and N = 40). Functional analyses of emerging genes were performed through siRNA in different subpopulation of PM cells, growing under hypoxia.
    RESULTS: A copy number gain of NOTCH2 was observed in 50% of patients with progressive disease and its overexpression correlated with a worse prognosis in both pemetrexed-treated and untreated-patients' cohorts. Conversely, losses of PTP4A3 correlated with clinical benefit, while patients with overexpression of both NOTCH2 and PTP4A3 had the worse prognosis. Moreover, NOTCH2 silencing through siRNA in vitro reduced migration, enhancing apoptosis of PM cells, while the PTP4A3 inhibitor BR-1 overcame pemetrexed resistance in PM cells characterized by high NOTCH2/PTP4A3 expression.
    CONCLUSIONS: NOTCH2 and PTP4A3 alterations are associated with clinical outcomes in pemetrexed-treated PM patients. The inhibition of NOTCH pathway may be exploited to eradicate CSCs and improve patients' survival.
    Keywords:  Biomarkers; Hypoxia; Mesothelioma; NOTCH; PTP4A3
    DOI:  https://doi.org/10.1016/j.lungcan.2024.108024
  4. Gen Thorac Cardiovasc Surg Cases. 2024 Jun 11. 3(1): 31
      BACKGROUND: Pleural mesothelioma, characterized by a dismal prognosis even with multimodal therapy, has seen emerging interest in immune checkpoint inhibitors (ICIs) due to their demonstrated efficacy. Here, we present a case of epithelioid-type pleural mesothelioma with chest wall invasion treated with definitive ICI therapy, resulting in a remarkable pretreatment effect.CASE PRESENTATION: A 46-year-old man was diagnosed with an abnormal chest shadow on a medical check, and a computed tomography scan showed pleural thickening at the dorsal right upper chest wall. One of the nodules was suspected to have invaded the chest wall. A needle biopsy revealed epithelioid-type pleural mesothelioma. After five cycles of nivolumab plus ipilimumab, he underwent right pleurectomy/decortication (P/D). Pathological examination revealed a significant treatment effect, showing numerous lymphocytes infiltrating the tumor nodule and viable tumor cells localized at approximately 6 mm.
    CONCLUSION: Although further accumulation of cases is required to evaluate the effectiveness and case selection, P/D after immunotherapy is a useful curative treatment option for advanced pleural mesothelioma.
    Keywords:  Immune checkpoint inhibitor; Pleural mesothelioma; Pleurectomy/decortication; Salvage surgery
    DOI:  https://doi.org/10.1186/s44215-024-00157-3
  5. J Int Med Res. 2024 Nov;52(11): 3000605241287320
      Malignant mesothelioma is a rare highly invasive tumour originating from the mesothelial cells of the pleura, peritoneum and pericardium. Malignant pleural mesothelioma (MPM) is the most common type in all malignant mesothelioma. The onset of MPM is associated with exposure to asbestos and it can have an incubation period of up to 40 years. The incidence of MPM has been increasing worldwide in recent years, so more attention has been focused on its diagnosis, treatment and prognosis. Activating mutations, amplifications and fusions/rearrangements of the anaplastic lymphoma kinase receptor tyrosine kinase (ALK) gene are commonly seen in patients with non-small cell lung cancer. However, it is rare in MPM. This current case report describes a female patient with advanced MPM with an ALK gene fusion mutation. In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.
    Keywords:  CDKN2A; Malignant pleural mesothelioma (MPM); anaplastic lymphoma kinase gene; case report; crizotinib
    DOI:  https://doi.org/10.1177/03000605241287320
  6. ACS Pharmacol Transl Sci. 2024 Nov 08. 7(11): 3299-3333
      Pleural mesothelioma (PM), a rare malignant tumor explicitly associated with asbestos and erionite exposures, has become a global health problem due to limited treatment options and a poor prognosis, in which the median life expectancy varies depending on the method of treatment. However, the importance of early diagnosis is emphasized, and the practical methods have not matured yet. This study provides a critical overview of PM, addressing various aspects like epidemiology, etiology, diagnosis, treatment options, and the potential use of advanced technologies like microfluidic chip-based models for research and diagnosis. It initially begins with fundamentals of clinical aspects and then discusses the identification of disease-specific biomarkers in patients' serum or plasma samples, which could potentially be used for early diagnosis. A detailed investigation of the sophisticated preclinical models is highlighted. Recent three-dimensional (3D) model accomplishments, including microarchitecture modeling by transwell coculture, spheroids, organoids, 3D bioprinting constructs, and ex vivo tumor slices, are discussed comprehensively. On-chip models that imitate physiological processes, such as detection chips and therapeutic screening chips, are assessed as potential techniques. The review concludes with a critical and constructive discussion of the growing interest in the topic and its limitations and suggestions.
    DOI:  https://doi.org/10.1021/acsptsci.4c00324
  7. BJC Rep. 2024 May 24. 2(1): 42
      BACKGROUND: Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of ~2.5 years.METHODS: We 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.
    RESULTS: The 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.
    CONCLUSIONS: Our findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results.
    DOI:  https://doi.org/10.1038/s44276-024-00062-w
  8. BJC Rep. 2023 Jun 22. 1(1): 4
      BACKGROUND: Malignant mesothelioma is a tumour that is strongly associated with a history of asbestos exposure, and which derives from mesothelial cells that line the serous cavities of the body. The tumour most commonly arises in the pleural cavity, but can also arise in the pericardium, peritoneum, and tunica vaginalis. At present the lesion has a very poor prognosis and is an incurable form of cancer with median survival times of up to 19 months being quoted for some histological subtypes. A large proportion of mesotheliomas have been shown to be arginine auxotrophic, leading to new research for therapeutics which might exploit this potential vulnerability.METHODS: We measured the levels of General Control Non-derepressible 2 (GCN2) protein in malignant mesothelioma tumour samples and determined whether these levels correlate with clinical outcomes.
    RESULTS: We observed that the expression levels of GCN2 correlated with patient survival and was an independent prognostic variable in pairwise comparisons with all available clinical data.
    CONCLUSION: These findings suggest that GCN2 levels provides prognostic information and may allow for stratification of care pathways. It may suggest that targeting GCN2 is a viable strategy for mesothelioma therapy development.
    DOI:  https://doi.org/10.1038/s44276-023-00004-y