Biphasic mesothelioma (BM) is an uncommon and especially severe subtype of malignant mesothelioma and is defined by its heterogeneous histological composition. To aid in the diagnosis and the development of therapeutics for biphasic mesothelioma, Protheragen offers an all-inclusive suite of services. At Protheragen, we have an integrated system that includes advanced technologies and professional scientific consultancy to solve the problem of biphasic mesothelioma research.
Overview of Biphasic Mesothelioma (BM)
Biphasic mesothelioma (BM) is a subtype of malignant mesothelioma (MM) that is diagnosed by the simultaneous presence of both epithelioid and sarcomatoid portions cross-sectionally and is considered a dual morphology. The World Health Organization (WHO) stipulates a minimum of 10% of each component for a tumor to be diagnosed as BM. The epithelial component comprises polygonal cells with abundant eosinophilic cytoplasm and vesicular nuclei, while the sarcomatoid portion consists of spindle-shaped cells with significant nuclear atypia and a high mitotic index. BM is notable for an aggressive course and very poor prognosis, which is allied with intermediate survival rates between those of pure epithelioid and sarcomatoid mesotheliomas.
Fig.1 Results from 147 successive patients diagnosed with biphasic mesothelioma, who underwent planned pleurectomy decortication (PDC) over an 11-year period, are presented. (Lapidot M.,
et al., 2022)
Diagnostics Development for Biphasic Mesothelioma (BM)
Histopathological Diagnosis
For the BM, the basic H and E (Hematoxylin and Eosin) staining helps in the evaluation of cellular structures and the detection of both epithelioid and sarcomatoid components. Differentiation of the tumor from other tumors and confirmation of the tumor arising from mesothelium is done with the help of IHC. To demonstrate the epithelioid components of the tumor, the immunohistochemical markers calretinin, WT1, and pan-cytokeratin are utilized. For the diagnosis of the sarcomatoid component, BAP1 loss and CDKN2A (p16) deletion are diagnosed.
Molecular Analysis
Molecular diagnostics are vital when diagnosing abnormalities in biphasic mesothelioma (BM). One hallmark of malignancy is the spindle cell component’s CDKN2A (p16) homozygous deletion, which is detectable via fluorescence in situ hybridization (FISH). Also, next-generation sequencing (NGS) identifies particular genetic changes and mutations that may inform targeted therapy. For example, the loss of BAP1 is a frequent occurrence in mesotheliomas and is detectable by IHC or through other molecular methods.
Therapeutics Development for Biphasic Mesothelioma (BM)
- Immunotherapy
Immunotherapy is emerging as a potential therapeutic option for mesothelioma and all its variants, including BM. Immune checkpoint inhibitors like nivolumab and ipilimumab, administered as anti-PD-1 and anti-CTLA-4, respectively, have proven to be effective in increasing survival rates in patients suffering from advanced mesothelioma. These medications improve outcomes by bolstering the systemic immune defense mechanisms employed by the body to fight tumor cells. Clinical studies are testing the use of combined chemotherapy and immunotherapy for BM, and the preliminary findings are very promising.
- Targeted Therapy
Targeted therapies seek to block specific molecular pathways related to the progression of BM. One example is the targeting of the BAP1 pathway since loss of BAP1 is a major driver of BM tumor progression. Clinical trials are testing the application of small-molecule and monoclonal antibody inhibitors that are specific to these molecular changes. Another relevant and rapidly developing approach is targeting the FGFR pathway since it is also involved in tumor angiogenesis.
Table 1. Overview of preclinical studies of genetic therapy in mesothelioma. (Štrbac D., et al., 2022)
| Used Therapeutic Agent |
Endpoints of the Study |
Major Findings |
Type of Study |
| Pladienolide-B, E7107, Meayamycin-B |
To investigate whether splicing modulators are capable of modifying the cell cycle and apoptosis. |
Splicing modulators compromise the viability of mesothelioma cancer cells. |
Preclinical, mesothelioma cell lines |
| miR-15/16 |
To investigate the suppression of fibroblast growth factor (FGF) expression mediated by miR-15/16. |
miR-15/16 can downregulate FGF and inhibit the growth of mesothelioma cells. |
Preclinical, mesothelioma cell lines |
| DFP-10825 (shRNA) |
To explore whether cationic liposomes carrying shRNA targeting thymidylate synthase can suppress cell proliferation in peritoneal mesothelioma. |
High therapeutic effect without severe side effects. |
Preclinical, mouse model |
| miR-137 |
To investigate whether the Y box binding protein 1 gene (YBX1) is capable of reducing miR-137 levels in mesothelioma. |
The combination of miR-137 and YBX1 can inhibit the proliferation, invasion, and migration of mesothelioma cells. |
Preclinical, mesothelioma cell lines |
| miR-126 |
To investigate whether the restoration of miR-126 expression can suppress cell invasion and proliferation. |
MiR-126 induces G1/S cell cycle arrest and inhibits proliferation. |
Preclinical, mesothelioma cell lines |
| miR-182/miR-183 |
To examine whether suppressing miR-182/miR-183 can attenuate the proliferation and migration capabilities of mesothelioma cells. |
miR-182/miR-183 inhibitors can reduce the proliferation and migration of mesothelioma cells. |
Preclinical, mesothelioma cell lines |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragenoffers comprehensive services for the development of diagnostics and therapeutics for biphasic mesothelioma. Our expertise spans from histopathological and molecular diagnostics to the development of targeted therapies and immunotherapeutics. Our preclinical research services include the evaluation of novel drugs and combination therapies in relevant models of biphasic mesothelioma.
Disease Models
- Cell Line Models
- Organoid Models
- Intrapleural Injection of Carbon Nanotube and Asbestos Models
- Transtracheal Intrapulmonary Spraying of Multiwalled CNT Models
- Subcutaneous PDX Models
Protheragen recognizes that each BM project is unique. Our customized services allow clients to select specific modules from our diagnostics and therapeutics development pipeline or design bespoke studies to meet their research objectives. Whether it's optimizing a diagnostic assay or advancing a novel therapeutic candidate through preclinical development, we provide flexible, scalable solutions to drive success. If you are interested in our services, please feel free to contact us.
References
- Lapidot, Moshe, Emanuele Mazzola, and Raphael Bueno. "Outcomes of pleurectomy decortication in patients with biphasic mesothelioma." The Journal of Thoracic and Cardiovascular Surgery 164.5 (2022): 1340-1348.
- Salle, F. Galateau, et al. "New insights on diagnostic reproducibility of biphasic mesotheliomas: a multi-institutional evaluation by the international mesothelioma panel from the MESOPATH reference center." Journal of thoracic oncology 13.8 (2018): 1189-1203.
- Štrbac, Danijela, and Vita Dolžan. "Novel and future treatment options in mesothelioma: a systematic review." International journal of molecular sciences 23.4 (2022): 1975.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
