Reference Detail

Ref Type

Journal Article

PMID

(39018564)

Authors

Martínez-Quintanilla J, Cabot D, Sabia D, Arqués O, PMPnet Group, Vergés J, Chicote I, Bijelic L, PMPnet Group, Cabellos L, Alcántara AM, Ramos I, Barrios P, Crusellas O, Palacio LM, PMPnet Group, Cámara JA, Barriuso J, PMPnet Group, Jiménez JJ, Muñoz-Torres P, Nonell L, Flores R, Médico E, Guaglio M, PMPnet Group, Ros J, Élez E, Tabernero J, Aziz O, Deraco M, Palmer HG, PMPnet Group, PMPnet Group

Title

Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research	30	18	2024 Sep 13	4082-4099	Clin Cancer Res

URL

Abstract Text

Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients.A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoid (PDO) and xenograft (PDX) models. Whole exome sequencing, immunohistochemistry analyses, and in vitro and in vivo drug efficacy studies were performed.In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C, and KRASG12D, that could also be detected in intra-abdominal mucin biopsies of patients with PMP using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models.Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for patients with BRAFV600E PMP who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to patients with PMP.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	pseudomyxoma peritonei	sensitive	Encorafenib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, Braftovi (encorafenib) inhibited viability and induced apoptosis in a patient-derived pseudomyxoma peritonei cell line harboring BRAF V600E in culture and inhibited tumor growth and improved survival of a patient-derived xenograft (PDX) model (PMID: 39018564).	39018564
BRAF V600E	pseudomyxoma peritonei	sensitive	Cetuximab + Encorafenib	Preclinical - Pdx & cell culture	Actionable	In a preclinical study, treatment with the combination of Braftovi (encorafenib) and Erbitux (cetuximab) inhibited viability and induced apoptosis in a patient-derived pseudomyxoma peritonei cell line harboring BRAF V600E in culture and inhibited tumor growth and improved survival of a patient-derived xenograft (PDX) model (PMID: 39018564).	39018564