Malignant Peritoneal Mesothelioma (MPM) is an extremely aggressive and invasive cancer that affects the serosal lining of the abdominal cavity. At Protheragen, we provide a full suite of services dedicated to the development of diagnostics and therapeutics for MPM. Our comprehensive strategy spans the entire development process, starting from initial target identification and validation through to preclinical validation.
Overview of Malignant Peritoneal Mesothelioma (MPM)
Malignant Peritoneal Mesothelioma (MPM) is a rare and aggressive malignancy originating from the mesothelial cells lining the peritoneum, the serous membrane that covers the intra-abdominal organs and abdominal wall. This disease is characterized by a diffuse and expansive pattern of growth within the abdominal cavity, often leading to significant morbidity and mortality. Historically, MPM was poorly understood, and therapeutic options were limited, resulting in poor patient outcomes. However, recent advancements in understanding its pathogenesis, diagnosis, and therapeutics have led to improved survival rates and better management strategies.
Fig.1 Peritoneal carcinoma index score. (Karpes J. B.,
et al., 2023)
Pathogenesis of Malignant Peritoneal Mesothelioma (MPM)
The development of MPM is influenced by multiple factors, including genetic mutations, environmental exposures, and inflammatory processes. Asbestos exposure is a recognized risk factor for MPM, although its association is not as strong as with pleural mesothelioma. When inhaled or ingested, asbestos fibers can induce DNA damage and genomic instability, resulting in chronic inflammation and the eventual development of malignancy. Common genetic mutations observed in MPM include alterations in tumor suppressor genes such as BAP1, CDKN2A, and NF2. Additionally, ALK rearrangements and overexpression of PD-L1 have been identified in some cases. Other risk factors for MPM include germline mutations, genetic syndromes, therapeutic irradiation, peritoneal irritation from previous surgeries, chronic peritonitis, autoimmune inflammatory processes, and exposure to certain viruses.
Diagnostics Development for Malignant Peritoneal Mesothelioma (MPM)
Tumor Markers
Serum tumor markers, such as Cancer Antigen (CA)-125 and CA15-3, are frequently elevated in MPM patients. While their sensitivity is relatively low, they can be useful in monitoring therapeutic response and recurrence. Other markers, including osteopontin and mesothelin-related protein (SMRP), are also being explored for their diagnostic potential.
Immunohistochemistry
mmunohistochemical (IHC) staining plays a crucial role in distinguishing MPM from other intra-abdominal malignancies. Characteristic positive stains for MPM include calretinin, WT-1, and cytokeratin 5/6, while negative stains for carcinoembryonic antigen (CEA) and other markers help confirm the diagnosis accurately.
Therapeutics Development for Malignant Peritoneal Mesothelioma (MPM)
Systemic chemotherapy remains a cornerstone of MPM therapy. The combination of pemetrexed and cisplatin is the standard first-line regimen, demonstrating improved survival rates compared to cisplatin alone. Second-line options include pemetrexed and gemcitabine for patients who cannot tolerate platinum therapy.
Targeted therapies and immunotherapies represent the frontier of MPM therapy. ALK inhibitors, such as alectinib, have shown promise in patients with ALK-positive MPM. Immunotherapies, including PD-1 inhibitors like nivolumab, are being explored for their potential to enhance the immune response against MPM.
Table 1. Therapeutics of Malignant Peritoneal Mesothelioma (MPM).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Chemotherapy |
Pemetrexed |
DNA synthesis and repair |
Inhibits thymidylate synthase, glycinamide ribonucleotide formyltransferase, and purine synthesis |
Approved |
| Cisplatin |
DNA cross-linking |
Forms intrastrand and interstrand DNA cross-links, leading to cell death |
Approved |
| Gemcitabine |
DNA synthesis |
Inhibits DNA synthesis by incorporating into DNA |
Approved |
| Targeted Therapy |
Alectinib |
ALK (Anaplastic Lymphoma Kinase) |
Tyrosine kinase inhibitor targeting ALK rearrangements |
Phase II |
| NA |
EGFR (Epidermal Growth Factor Receptor) |
Tyrosine kinase inhibitor targeting EGFR overexpression |
Preclinical |
| NA |
EGFR (Epidermal Growth Factor Receptor) |
Tyrosine kinase inhibitor targeting EGFR overexpression |
Preclinical |
| NA |
VEGF (Vascular Endothelial Growth Factor) |
Angiokinase inhibitor targeting VEGF receptors |
Preclinical |
| Immunotherapy |
NA |
CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4) |
Monoclonal antibody targeting CTLA-4 enhances T-cell activity |
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 comprehensive therapeutic development services for MPM, leveraging cutting-edge technologies and expertise in oncology research. Our services include a broad range of diagnostic and therapeutic approaches to meet the unique needs of our clients.
Disease Models
- Primary MPM Cell Lines
- Organoids from Animal Models
- Patient-Derived Xenograft (PDX) Models
- MPM-Prone Genetically Modified Mouse Models
- Asbestos-Induced Mouse Models
Protheragen's preclinical research services for MPM include in vitro and in vivo models to evaluate the efficacy and safety of potential therapeutic agents. Our state-of-the-art facilities and experienced research team enable us to conduct high-throughput screening, pharmacokinetic and pharmacodynamic studies, and toxicity assessments, providing valuable data to support clinical development. If you are interested in our services, please feel free to contact us.
Reference
- Karpes, Josh B., et al. "Malignant peritoneal mesothelioma: an in-depth and up-to-date review of pathogenesis, diagnosis, management and future directions." Cancers 15.19 (2023): 4704.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
