Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment.

YAP breast cancer dasatinib drug testing heterogeneity mechanotransduction patient-derived tumor organoids statin

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
21 Dec 2020
Historique:
received: 15 10 2020
revised: 15 12 2020
accepted: 17 12 2020
entrez: 29 12 2020
pubmed: 30 12 2020
medline: 30 12 2020
Statut: epublish

Résumé

Tumor organoids are tridimensional cell culture systems that are generated in vitro from surgically resected patients' tumors. They can be propagated in culture maintaining several features of the tumor of origin, including cellular and genetic heterogeneity, thus representing a promising tool for precision cancer medicine. Here, we established patient-derived tumor organoids (PDOs) from different breast cancer subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple negative). The established model systems showed histological and genomic concordance with parental tumors. However, in PDOs, the ratio of diverse cell populations was frequently different from that originally observed in parental tumors. We showed that tumor organoids represent a valuable system to test the efficacy of standard therapeutic treatments and to identify drug resistant populations within tumors. We also report that inhibitors of mechanosignaling and of Yes-associated protein 1 (YAP) activation can restore chemosensitivity in drug resistant tumor organoids.

Identifiants

pubmed: 33371412
pii: cancers12123869
doi: 10.3390/cancers12123869
pmc: PMC7770601
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : European Union, European Regional Development Fund and Interreg V-A Italia-Austria 2014-2020
ID : ITAT1096-P
Organisme : Italian University and Research Ministry
ID : PRIN-2017HWTP2K_004
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 22174
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 22759
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : 10016

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Auteurs

Elena Campaner (E)

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
National Laboratory CIB (LNCIB), Area Science Park-Padriciano, 34149 Trieste, Italy.

Alessandro Zannini (A)

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
National Laboratory CIB (LNCIB), Area Science Park-Padriciano, 34149 Trieste, Italy.

Mariangela Santorsola (M)

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
National Laboratory CIB (LNCIB), Area Science Park-Padriciano, 34149 Trieste, Italy.

Deborah Bonazza (D)

Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy.
UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy.

Cristina Bottin (C)

Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy.
UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy.

Valeria Cancila (V)

Tumor Immunology Unit, Department of Health Science, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy.

Claudio Tripodo (C)

Tumor Immunology Unit, Department of Health Science, Human Pathology Section, School of Medicine, University of Palermo, 90133 Palermo, Italy.
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), 20139 Milano, Italy.

Marina Bortul (M)

Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy.
Breast Unit, Division of General Surgery, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy.

Fabrizio Zanconati (F)

Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, 34149 Trieste, Italy.
UCO Anatomia e Istologia Patologica, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Hospital of Cattinara, 34149 Trieste, Italy.

Stefan Schoeftner (S)

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
National Laboratory CIB (LNCIB), Area Science Park-Padriciano, 34149 Trieste, Italy.

Giannino Del Sal (G)

Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
National Laboratory CIB (LNCIB), Area Science Park-Padriciano, 34149 Trieste, Italy.
Fondazione Istituto FIRC di Oncologia Molecolare (IFOM), 20139 Milano, Italy.

Classifications MeSH