Pseudomyxoma Peritonei (PMP) is a highly complex and formidable malignancy that poses a significant challenge in the field of oncology. At Protheragen, we are at the cutting edge of developing innovative preclinical solutions specifically tailored to address this rare and intricate disease. Our extensive experience in biological research and drug development, coupled with our in-depth understanding of the intricacies of PMP, uniquely positions us to make a substantial and meaningful contribution to the PMP landscape.
Overview of Pseudomyxoma Peritonei (PMP)
Pseudomyxoma Peritonei (PMP) is a rare and intricate malignancy that originates primarily from the appendix. It is characterized by the extensive spread of mucin-producing tumor cells throughout the abdominal cavity. This leads to the accumulation of vast quantities of mucinous material, which in turn causes significant abdominal distension, intestinal obstruction, and subsequent morbidity. It often presents with symptoms such as abdominal pain, bloating, and weight loss, all of which tend to progressively worsen over time.
Fig.1 Main pathways involved in mucin expression in PMP. (Sommariva A.,
et al., 2021)
Pathogenesis of Pseudomyxoma Peritonei (PMP)
The pathogenesis of Pseudomyxoma Peritonei (PMP) is complex and multifactorial, encompassing genetic alterations and mucin overproduction. Genetic mutations in KRAS and GNAS have emerged as pivotal drivers of mucin production and tumor progression. These mutations trigger the activation of signaling pathways that significantly amplify mucin synthesis and secretion. Moreover, the inflammatory microenvironment within the peritoneal cavity exerts a profound influence, fostering tumor growth and mucin production. The intricate interplay between genetic factors and the tumor microenvironment orchestrates a highly complex landscape that propels the development and progression of PMP.
Diagnostics Development for Pseudomyxoma Peritonei (PMP)
Histopathological Analysis
Histopathological examination of tissue samples is fundamental for confirming the diagnosis of PMP and determining its grade. The presence of mucin-producing tumor cells and the degree of cellular atypia are key features assessed by pathologists. The 2016 Peritoneal Surface Oncology Group International (PSOGI) classification system categorizes PMP into four types: acellular mucin, low-grade mucinous carcinoma peritonei (LMCP), high-grade mucinous carcinoma peritonei (HMCP), and HMCP with signet ring cells. This classification aids in therapeutic planning and prognostic assessment.
Molecular Markers
With the progress of molecular diagnostic techniques, potential biomarkers for Pseudomyxoma Peritonei (PMP) have been identified. Genetic mutations in KRAS and GNAS are commonly found in PMP tissues, which helps to understand the disease's biological characteristics and provides potential therapeutic targets. Moreover, the expression of mucin genes, such as MUC2, MUC5AC, and MUC6, is being investigated as diagnostic and prognostic indicators. These molecular markers are expected to facilitate early detection and personalized therapeutic strategies.
Therapeutics Development for Pseudomyxoma Peritonei (PMP)
- Systemic Chemotherapy: Systemic chemotherapy may be used as adjuvant therapy after CRS-HIPEC or as palliative therapy for cases with unresectable or recurrent disease. Commonly used regimens include fluoropyrimidines (e.g., 5-fluorouracil) combined with alkylating agents (e.g., oxaliplatin).
- Targeted Therapy: Given the genetic alterations observed in PMP, targeted therapies against specific molecular pathways, such as EGFR or VEGF inhibitors, are being explored.
- Immunotherapy: Immunotherapy, including immune checkpoint inhibitors, is also under investigation for the therapeutic of PMP, particularly in cases with microsatellite instability-high (MSI-H) tumors.
Table 1. Therapeutics of Pseudomyxoma Peritonei (PMP).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Systemic Chemotherapy |
5-Fluorouracil (5-FU) |
Tumor cells |
Used in combination with other drugs for systemic chemotherapy. |
Approved |
| Systemic Chemotherapy |
Oxaliplatin |
Tumor cells |
Used in combination with 5-FU and leucovorin for systemic chemotherapy. |
Approved |
| Systemic Chemotherapy |
Mitomycin C (MMC) |
Tumor cells |
Used in HIPEC and systemic chemotherapy. |
Approved |
| Systemic Chemotherapy |
Capecitabine |
Tumor cells |
Oral chemotherapy is used in combination with MMC or other agents. |
Approved |
| Systemic Chemotherapy |
Bevacizumab |
VEGF |
Anti-angiogenic therapy targeting VEGF to inhibit tumor blood vessel formation. |
Approved |
| Mucolytic Agents |
N-Acetylcysteine (NAC) |
Mucin |
Mucolytic agent that reduces mucin viscosity and has antioxidant properties. |
Phase I |
| Mucolytic Agents |
Bromelain |
Mucin |
Enzyme mixture with mucolytic and anti-inflammatory properties. |
Phase I |
| Targeted Therapy |
RDEA119 (BAY 86-9766) |
MEK1/2 |
MEK1/2 inhibitor shown to reduce MUC2 transcription and inhibit tumor growth in preclinical models. |
Preclinical studies |
| Other Therapies |
Bortezomib |
Proteasome |
Proteasome inhibitors are used to induce apoptosis in tumor cells. |
Preclinical studies |
| Other Therapies |
HRF-3 |
Proteasome |
UPS inhibitor with cytotoxic properties in cancer cells. |
Preclinical studies |
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 all-encompassing preclinical therapeutic development services for PMP, harnessing state-of-the-art technologies and a team of cross-disciplinary experts. Our offerings span the entire spectrum of PMP diagnostics and therapeutic development, ranging from early-stage discovery to preclinical testing and further stages.
Disease Models
- N14A and N15A Cell Lines
- NCC-PMP1-C1 Cell Lines
- Patient-Derived Organoids (PDOs)
- Orthotopic Xenograft Models
Protheragen provides a full spectrum of preclinical research services crucial for advancing PMP therapies. This includes the development and utilization of relevant in vitro and in vivo models that accurately recapitulate the disease pathology. If you are interested in our services, please feel free to contact us.
References
- Sommariva, Antonio, et al. "Novel perspectives in pseudomyxoma peritonei treatment." Cancers 13.23 (2021): 5965.
- Lin, Yu-Lin, et al. "Consensuses and controversies on pseudomyxoma peritonei: a review of the published consensus statements and guidelines." Orphanet Journal of Rare Diseases 16 (2021): 1-17.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
