Diffuse Malignant Peritoneal Mesothelioma (DMPM) is a rare, aggressive form of cancer arising from the mesothelioma cells of the peritoneal cavity. Using advanced technologies and a multidisciplinary approach, Protheragen provides full-service diagnostics and therapeutics development for DMPM.
Overview of Diffuse Malignant Peritoneal Mesothelioma (DMPM)
Diffuse Malignant Peritoneal Mesothelioma (DMPM) is an uncommon and metastatic type of cancer that develops from the peritoneum, which is the tissue lining the inside of the abdominal cavity. The malignant tumor cells in DMPM are characterized by a diffuse, invasive peritoneal growth, which is the most common cause of abdominal and pelvic cancer-related morbidity and mortality. It forms 15% of all mesotheliomas and, unlike the pleural mesothelioma, is diagnosed in younger patients. It is also diagnosed in males and females in equal numbers. The symptoms of DMPM, which commonly abdominal pain, abdominal distention, ascites, and weight loss, are quite nonspecific. It is the result of a considerable delay in diagnosis, often due to the late stage of the disease at diagnosis.
Fig.1 Diagnostic and therapeutic pathway in diffuse malignant peritoneal mesothelioma. (Kusamura S.,
et al., 2023)
Diagnostics Development for Diffuse Malignant Peritoneal Mesothelioma (DMPM)
Immunohistochemistry (IHC) Diagnostics
IHC remains a cornerstone in the diagnosis of DMPM. It involves the use of antibodies to detect specific biomarkers expressed in tumor cells, providing vital information about tumor origin and differentiation. Key markers for DMPM include WT1, calretinin, and D2-40, which are highly expressed in mesothelial cells. Additionally, the lack of BAP1 expression in tumors can be indicative of malignancy.
Imaging Techniques
As part of the preoperative assessment, imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI) are very important as they determine the extent of peritoneal disease and any metastasis. CT imaging identifies characteristic features that include mesenteric thickening, peritoneal plaques, and ascites. More recently, it has been suggested that 18F-FDG PET/CT is useful for more accurate disease staging and for detecting recurrence, which assists in better planning of therapy.
Biomarker Discovery
Work continues to find DMPM-specific biomarkers to enable more accurate early diagnosis. Patients with mesothelioma frequently have elevated serum mesothelin levels, which are being evaluated as a diagnostic marker. CA-125 is another serum marker that seems to aid in predicting disease progression as well as in evaluating the effectiveness of therapeutic. However, the sensitivity and specificity of CA-125 for DMPM remain under evaluation.
Therapeutics Development for Diffuse Malignant Peritoneal Mesothelioma (DMPM)
- Immunotherapy
Research is exploring the use of ICIs for immunotherapy as a therapeutic for DMPM. Although nivolumab and pembrolizumab are ICIs that are used with some success for other forms of mesothelioma, their use in DMPM is yet to be proven. There are clinical trials of ICIs in DMPM, and the results are not uniform; some studies have observed that some patients achieved better progression-free survival with these therapeutics.
- Targeted Molecular Therapy
Research focus in the area of DMPM therapeutic is given regarding the development of targeted molecular therapies. Specifically, therapeutics that aim at the PI3K/AKT/mTOR signaling pathway are being developed. Also, some therapies which RTK receptors Axl, MET, and EGFR are being used are try to block the metastatic and invasive growth of the tumor cells in preclinical and clinical stages. Preliminary studies suggest that DMPM tumor growth and metastasis may be inhibited using these pathways.
Table 1. Therapeutics of diffuse malignant peritoneal mesothelioma (DMPM). (Kusamura S., et al., 2023)
| Therapeutics |
Drug Name |
Mechanism |
Description |
Stage |
| Cytoreductive Surgery (CRS) |
N/A |
Surgical removal of the visible tumor |
CRS aims to remove all visible tumor tissue, reducing the tumor burden and improving the efficacy of subsequent therapeutics. |
Approved |
| Hyperthermic Intraperitoneal Chemotherapy (HIPEC) |
Cisplatin, Doxorubicin, Mitomycin-C |
High-dose chemotherapy delivered directly to the peritoneal cavity under hyperthermic conditions |
Enhances the cytotoxicity of chemotherapeutic agents, targeting residual microscopic disease. |
Approved |
| Systemic Chemotherapy |
Pemetrexed, Cisplatin |
Inhibition of folate-dependent enzymes |
Pemetrexed disrupts DNA synthesis and repair, while cisplatin forms DNA adducts, leading to cell death. |
Approved |
| Peritoneal Chemotherapy |
Cisplatin, Gemcitabine, Pemetrexed |
Local delivery of chemotherapy |
Postoperative intraperitoneal chemotherapy (EPIC) and non-hyperthermic intraperitoneal chemotherapy (NIPEC) to target residual disease. |
Approved |
| Immunotherapy |
Atezolizumab (PD-L1 inhibitor), Bevacizumab (VEGF inhibitor) |
Immune checkpoint inhibition and anti-angiogenesis |
Atezolizumab blocks PD-L1, enhancing T-cell activity against tumor cells. Bevacizumab inhibits VEGF, reducing tumor blood supply. |
Phase II |
| Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) |
Cisplatin, Gemcitabine |
Aerosolized chemotherapy delivered under pressure |
Enhances drug penetration and distribution within the peritoneal cavity. |
Phase II |
| Targeted Molecular Therapy |
N/A |
Targeting specific molecular pathways |
Inhibition of the PI3K/AKT/mTOR signaling pathway, ERBB1/ERBB2/ERBB3, and other receptor tyrosine kinases (RTKs) involved in DMPM. |
Preclinical |
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
Protheragen provides a comprehensive range of services for the development of diagnostics and therapeutics for DMPM. Our offerings include advanced imaging technologies, detailed histopathological analysis, and extensive preclinical research. We specialize in the development of targeted therapies and immunotherapies, utilizing our expertise in molecular biology and immunology to support innovative therapeutic solutions.
Disease Models
- Primary Cell Cultures
- Organoid Models
- Orthotopic Xenograft Mouse Models
- SV40 Virus-Induced Hamster Models
- v-src DNA Inoculation Chicken Models
Protheragen offers customized services for the development of diagnostics and therapeutics for DMPM. We customize our solutions to align with each client's distinct needs, ensuring the most effective and tailored approach for their specific goals. If you are interested in our services, please feel free to contact us.
References
- Kusamura, Shigeki, et al. "Diagnostic and therapeutic pathway in diffuse malignant peritoneal mesothelioma." Cancers 15.3 (2023): 662.
- Sun, Luanbiao, Chenguang Li, and Shuohui Gao. "Diffuse malignant peritoneal mesothelioma: a review." Frontiers in Surgery 9 (2023): 1015884.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
