Good News for Rare Disease Day and Every Day: Promising Lead on New Treatment for Pseudomyxoma Peritonei (PMP) — Written by: Deborah Shelton, ACPMP Executive Director

ACPMP Executive Director, Deborah Shelton, has over 25 years of experience providing regulatory advice to a diverse group of stakeholders navigating the complex landscape of scientific and clinical research directed at the development of treatments for cancer and a wide range of other conditions, with a particular focus on rare diseases.

In research funded with grant support from the ACPMP Research Foundation, clinicians and scientists at Oslo University have identified a potential new strategy for treating Pseudomyxoma Peritonei (PMP). As our readers know, there is critical need for ways to treat non-resectable and recurrent forms of this rare disease.

This grant was issued in 2019 in memory of Mike Liguori, Alexander Dalis,
Rick Dodson, 
George Haskin, Tammy Glawson, Karen Davis Redner, Jim Cain,
Stephen Thiesfeld,
Jay Verbos, Sharon Perry Delaney and Ray Ruliffson.

In the publication, Peptide vaccine targeted mutated GNAS: a potential novel treatment for pseudomyxoma peritonei, the authors report that the results of their recent study demonstrate a scientific basis for a vaccine to target GNAS-mutated tumors.


This is a promising development, as the GNAS gene is frequently mutated in PMP patients. In the study, mutated GNAS was detected in 22 out of 25 (88%) of tumor samples. Other published literature similarly reports a significantly high frequency of GNAS mutations in PMP (60-80%). To date, however, scientists have not yet developed a therapy targeting this mutation. The authors of this study note that although some cancers have certain mutations that can be targeted with drugs such as inhibitors and antibodies, targeting GNAS has proved especially challenging.


The good news, according to the authors, is that a vaccination approach may offer a viable path forward. The authors posit that the study findings provide a scientific rationale for exploring vaccination in combination with immune checkpoint inhibition as a possible curative treatment for PMP.


This rationale for the proposed vaccination strategy is detailed in the publication. This research is also further discussed in a recent webinar by Professor Flatmark, hosted by EuroPMP COST Action.


In brief, based on the findings of this study in which PMP tumor tissue was collected and T cells stimulated with the mutated GNAS product, the authors conclude that: (1) mutated GNAS in PMP generates a pre-existing immune response, but (2) that response is insufficient to control tumor growth, possibly due to inhibition caused by immune checkpoint inhibitor molecules found on the surface of the tumor-infiltrating T cells.


Based on these findings, the authors hypothesize that vaccination with the mutated GNAS product¹ will amplify the patient’s existing immune response and induce new T cells to respond, resulting in an expanded replication or cloning of T cells that recognize and target the mutated GNAS. The authors further hypothesize that this anti-tumor response could be bolstered by adding an immune checkpoint inhibitor to restore a fully functional immune response.


A small Phase 1 clinical trial is the next step. The “Pseudovax” trial  is expected to be a single-site study in Norway, enrolling approximately 10-20 patients. As with all Phase 1 studies,  the primary focus of this study will be to collect safety data. It is hoped, however, that the results of that Phase 1 clinical trial will provide a basis for extended future studies.


This study’s success demonstrates yet again the importance of funding research for appendix cancer. Solely through the generosity of our donors, the ACPMP Research Foundation has supported this and other critical research through its Research Grant Program (currently administered by the National Organization for Rare Diseases (NORD)).


To the clinicians and scientists, the ACPMP Research Foundation, and the courageous community we serve, sincerely thank you for all that you are doing. We are stronger together!

Pictured: Professor Flatmark, Principal Investigator and lead author of the study discussed in this publication, and Jerry Lewandowski, ACPMP President, at PSOGI in 2018.

¹The mutated GNAS gene product identified is Gsαs. For the sake of simplicity, this product is referred to herein as mutated GNAS. For additional context, however, Gsα is a protein encoded by GNAS. It functions as a switch to control cell growth, survival and movement. Its mutation and related downstream signaling is thought to be a possible explanation for the excessive production of mucin in PMP.