Pseudomyxoma Peritonei, more commonly known as PMP is a very rare malignancy, affecting 1 to 3 cases per 1.000.000/year (World J Gastrointest Surg 2018;10:49). The most common site of origin is represented by the appendix, where a small number of mutated cells may start to secrete mucine, a jelly-like substance. Left untreated, these neoplastic mucinous cells may break in the abdominal cavity where they keep on producing more and more mucine and developing, over the years, the characteristic ‘jelly belly’, which could bring to clinical suggestive diagnosis, later confirmed by more fine tests and procedures 1,2.

When previous appendiceal and/or abdomen surgery samples are available, clinicians recur to histologic revision made by an expert pathologist to confirm PMP diagnosis. Otherwise, gold standard tool is based on chest-abdominal-pelvic computed tomography (CAP-CT) findings which might highlight the characteristic distribution pattern of mucinous ascites. Differently from other tumors, carcinoembryonic antigen and CA19-9 tumor markers, rather than being specific for PMP diagnosis, are usually used to follow PMP progression after treatment.

Currently, complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is considered the standard of care for those tumors that have invaded the abdominal cavity. The entire operation could last as much as 14 hours, but the duration usually decreases to 8 hours when surgery is performed by an expert surgeon. Moreover, the success rate of the surgery highly increases with the expertise of the operating surgeon. The CRS phase consists of opening the abdominal cavity and removing any visible part of mucine, together with the neoplastic cells. Later, a heated chemotherapy perfusion is pumped directly into the abdominal cavity to reach even the most hidden places and to kill any remaining cancer cells. When a 90 minute cycle of perfusion is passed, the perfusate is drained off, and the operation can be ended by the closing of the abdominal cavity. CRS-HIPEC confers an overall survival benefit of up to 63% at 10 years 3. However, the management of patients experiencing recurrence remains uncertain as no standard systemic treatment (sCT) is currently available, and even advanced diseases are orphan of an effective cure.

Due to PMP’s rarity and the difficulties in performing molecular and cellular studies on the few neoplastic cells, scientific knowledge is not progressing, thus the study of the cellular and omics fields in the PMP onset and progression are extremely hard.

The Accelerator Award enabled the synergic merger between the main four institutions highly specialized in Peritoneal Surface Malignancies (PSM) across UK, Spain, and Italy to investigate this extremely rare disease. The PMPnet International Team is looking for translational outcomes like prognostic tools, omics platforms and new chemotherapy resources which will hopefully change the research landscape. The PMPnet Team is taking advance from the state-of-the-art NGS techniques to build the largest series of PMP omics data from patients prospectively and retrospectively enrolled ensuring high quality of clinical data. The omic database will be made public and open to the scientific community after data processing on cBioportal, in accordance with its guidelines. The omic data will serve to identify molecular prognostic factors and prognostic scores, based on gene expression profiling, to better stratify PMP patients and to support therapeutic decision making. In addition, the PMPnet Team will develop 3D cell models, know as organoids, of PMP starting from neoplastic cells isolated from patients’ tissue. The patient-derived organoids will let us able to gain insight into the biology underlying PMP and to identify key regulatory networks that sustain its progression. The innovative development of organoids will allow different approaches to be tested in parallel at the PMPnet laboratories, leading to the identification of robust protocols to understand PMP and test new therapeutic strategies.

Eventually, the combination of NGS data with cellular and pharmacological research would enable the standardization of systemic therapies, the validation of “druggable targets” to develop personalized therapies.