# Application of Mucolytic Therapy in Patient-Derived Models of Pseudomyxoma Peritonei

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $204,233

## Abstract

Abstract
Pseudomyxoma peritonei (PMP), an insidious but lethal malignancy, refers to peritoneal metastases from
mucinous appendix neoplasms (MAN). PMP is poorly responsive to systemic chemotherapy and frequently
recurs despite aggressive and morbid locoregional surgical therapy. For low-grade PMP (LG-PMP), nearly all of
the deleterious clinical consequences are related to compressive organ dysfunction from excessive production
and intra-abdominal accumulation of paucicellular mucus (predominantly composed of mucin 2 [MUC2] protein).
Conversely, high-grade PMP (HG-PMP) is more cellular and invasive, and the abundant extracellular mucus
provides a protective environment for cancer cells to thrive. We hypothesize that reducing extracellular mucus
accumulation will minimize compressive organ dysfunction by decreasing the mucinous tumor burden of PMP
(especially LG-PMP) and improve the efficacy of chemotherapeutic or targeted drugs by removing the protective
mucus barrier surrounding neoplastic cells (especially HG-PMP). In this proposal, we will test the efficacy of
combinatorial mucolytic therapy, using bromelain (BR) + N-acetylcysteine (NAC), to dissolve extracellular mucus
in clinically relevant in vitro and in vivo patient-derived models of LG- and HG-MAN/PMP. Successful outcome
of the proposed studies will overcome a major hurdle for treating PMP, which is the mass-effect and
cytoprotective-effect of abundant extracellular mucus. In addition, our proposed research provides a novel
treatment dimension for PMP that may be applied to mucinous colorectal, pancreatic and ovarian cancers. Our
proposal is feasible since we are a major referral center for the management of patients with PMP, the proposed
drug combination effectively dissolves mucus in-silico, and we have developed in vitro and in vivo patient-derived
models of MAN/PMP that are representative of the clinical disease.

## Key facts

- **NIH application ID:** 9936370
- **Project number:** 5R21CA241004-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mohammad Haroon Asif Choudry
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,233
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936370

## Citation

> US National Institutes of Health, RePORTER application 9936370, Application of Mucolytic Therapy in Patient-Derived Models of Pseudomyxoma Peritonei (5R21CA241004-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9936370. Licensed CC0.

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