FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer - Sorbonne Université Access content directly
Journal Articles Digestive and Liver Disease Year : 2022

FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer

1 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
2 Institut Bergonié [Bordeaux]
3 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
4 FFCD - Fédération Francophone de Cancérologie Digestive
5 Service d'Oncologie médicale [CHU Henri Mondor]
6 IMRB - Institut Mondor de Recherche Biomédicale
7 Inserm U955 - Molecular virology and immunology – Physiopathology and therapeutic of chronic viral hepatitis (Team 18)
8 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
9 CHU Amiens-Picardie
10 UNIGE - Université de Genève = University of Geneva
11 CHU Dijon - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand
12 IPC - Institut Paoli-Calmettes
13 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
14 IDESP - Institut Desbrest de santé publique
15 AP-HP - Hopital Saint-Louis [AP-HP]
16 Hôpital Haut-Lévêque [CHU Bordeaux]
17 HCL - Hospices Civils de Lyon
18 LaTIM - Laboratoire de Traitement de l'Information Medicale
19 OSS - Oncogenesis, Stress, Signaling
20 CRLCC - CRLCC Eugène Marquis
21 Centre Hospitalier Universitaire [Rennes]
22 Hôpital Ambroise Paré [AP-HP]
23 BECCOH - Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie
24 HEGP - Hôpital Européen Georges Pompidou [APHP]
25 CHU Trousseau [Tours]
26 CRSA - Centre de Recherche Saint-Antoine
27 FHU PaCeMM - Paris Center for Microbiome Medicine
28 LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
Simon Pernot
Vincent Hautefeuille
Thomas Aparicio
Denis Smith
  • Function : Author
  • PersonId : 1025574
Claude Capron
  • Function : Author
  • PersonId : 936711
Theodora Bejan-Angoulvant
Julien Taieb
  • Function : Author
  • PersonId : 1138108

Abstract

The cellular prion protein PrP C partners with caveolin-1 (CAV1) in neurodegenerative diseases but whether this interplay occurs in cancer has never been investigated. By leveraging patient and cell line datasets, we uncover a molecular link between PrP C and CAV1 across cancer. Using cell-based assays, we show that PrP C regulates the expression of and interacts with CAV1. PrP C additionally controls the expression of the amyloid precursor protein APP and of the Aβ generating enzyme BACE1, and regulates the levels of Aβ, whose accumulation is a central event in Alzheimer’s disease. We further identify DKK1 and DKK3, involved in both Alzheimer’s disease and cancer progression, as targets of the PrP C -dependent axis. Finally, we establish that antibody-mediated blocking of the Aβ-PrP C interaction delays the growth of prostate cancer cell line-derived xenografts and prevents the development of metastases. Our data additionally support an enrichment of the Aβ-PrP C -dependent pathway in the basal subtype of prostate cancer, associated with anti-hormonal therapy resistance, and in mesenchymal colon cancer, associated with poor prognosis. Thus, based on a parallel with neurodegenerative diseases, our results bring to light an Aβ-PrP C axis and support the potential of targeting this pathway in patients with selected subtypes of prostate and colon cancer.
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Dates and versions

hal-03906999 , version 1 (24-01-2023)

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Violaine Randrian, Simon Pernot, Karine Le Malicot, Vittorio Catena, Isabelle Baumgaertner, et al.. FFCD 1709-SIRTCI phase II trial: Selective internal radiation therapy plus Xelox, Bevacizumab and Atezolizumab in liver-dominant metastatic colorectal cancer. Digestive and Liver Disease, 2022, 54 (7), pp.857-863. ⟨10.1016/j.dld.2022.04.024⟩. ⟨hal-03906999⟩
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