Literature DB >> 35174975

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

Lucía Zhu1, Diana Retana1, Pedro García-Gómez1, Laura Álvaro-Espinosa1, Neibla Priego1, Mariam Masmudi-Martín1, Natalia Yebra1, Lauritz Miarka1, Elena Hernández-Encinas2, Carmen Blanco-Aparicio2, Sonia Martínez2, Cecilia Sobrino3, Nuria Ajenjo3, Maria-Jesus Artiga3, Eva Ortega-Paino3, Raúl Torres-Ruiz4,5, Sandra Rodríguez-Perales4, Riccardo Soffietti6, Luca Bertero7, Paola Cassoni7, Tobias Weiss8, Javier Muñoz9, Juan Manuel Sepúlveda10, Pedro González-León11, Luis Jiménez-Roldán11,12,13, Luis Miguel Moreno11, Olga Esteban11, Ángel Pérez-Núñez11,12,14, Aurelio Hernández-Laín13, Oscar Toldos13, Yolanda Ruano15,16, Lucía Alcázar17, Guillermo Blasco17, José Fernández-Alén17, Eduardo Caleiras18, Miguel Lafarga19, Diego Megías20, Osvaldo Graña-Castro21, Carolina Nör22, Michael D Taylor22, Leonie S Young23, Damir Varešlija23, Nicola Cosgrove23, Fergus J Couch24, Lorena Cussó25,26,27,28, Manuel Desco25,26,27,28, Silvana Mouron29, Miguel Quintela-Fandino29, Michael Weller8, Joaquín Pastor2, Manuel Valiente1.   

Abstract

We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere.
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.

Entities:  

Keywords:  drug-screen; metastasis; organotypic cultures; patient-derived; resistance

Mesh：

Substances：

Year:  2022        PMID： 35174975      PMCID： PMC8899920          DOI： 10.15252/emmm.202114552

Source DB:  PubMed          Journal:  EMBO Mol Med        ISSN： 1757-4676            Impact factor:   12.137


  92 in total

Review 1.  Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and progression. A report from the RANO group.

Authors:  Nancy U Lin; Eudocia Q Lee; Hidefumi Aoyama; Igor J Barani; Brigitta G Baumert; Paul D Brown; D Ross Camidge; Susan M Chang; Janet Dancey; Laurie E Gaspar; Gordon J Harris; F Stephen Hodi; Steven N Kalkanis; Kathleen R Lamborn; Mark E Linskey; David R Macdonald; Kim Margolin; Minesh P Mehta; David Schiff; Riccardo Soffietti; John H Suh; Martin J van den Bent; Michael A Vogelbaum; Jeffrey S Wefel; Patrick Y Wen
Journal:  Lancet Oncol       Date:  2013-09       Impact factor: 41.316

2.  High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.

Authors:  Hui Gao; Joshua M Korn; Stéphane Ferretti; John E Monahan; Youzhen Wang; Mallika Singh; Chao Zhang; Christian Schnell; Guizhi Yang; Yun Zhang; O Alejandro Balbin; Stéphanie Barbe; Hongbo Cai; Fergal Casey; Susmita Chatterjee; Derek Y Chiang; Shannon Chuai; Shawn M Cogan; Scott D Collins; Ernesta Dammassa; Nicolas Ebel; Millicent Embry; John Green; Audrey Kauffmann; Colleen Kowal; Rebecca J Leary; Joseph Lehar; Ying Liang; Alice Loo; Edward Lorenzana; E Robert McDonald; Margaret E McLaughlin; Jason Merkin; Ronald Meyer; Tara L Naylor; Montesa Patawaran; Anupama Reddy; Claudia Röelli; David A Ruddy; Fernando Salangsang; Francesca Santacroce; Angad P Singh; Yan Tang; Walter Tinetto; Sonja Tobler; Roberto Velazquez; Kavitha Venkatesan; Fabian Von Arx; Hui Qin Wang; Zongyao Wang; Marion Wiesmann; Daniel Wyss; Fiona Xu; Hans Bitter; Peter Atadja; Emma Lees; Francesco Hofmann; En Li; Nicholas Keen; Robert Cozens; Michael Rugaard Jensen; Nancy K Pryer; Juliet A Williams; William R Sellers
Journal:  Nat Med       Date:  2015-10-19       Impact factor: 53.440

3.  EANO-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours.

Authors:  E Le Rhun; M Guckenberger; M Smits; R Dummer; T Bachelot; F Sahm; N Galldiks; E de Azambuja; A S Berghoff; P Metellus; S Peters; Y-K Hong; F Winkler; D Schadendorf; M van den Bent; J Seoane; R Stahel; G Minniti; P Wesseling; M Weller; M Preusser
Journal:  Ann Oncol       Date:  2021-08-05       Impact factor: 32.976

Review 4.  HSP90 and the chaperoning of cancer.

Authors:  Luke Whitesell; Susan L Lindquist
Journal:  Nat Rev Cancer       Date:  2005-10       Impact factor: 60.716

5.  Differential expression of HSP90 isoforms and their correlations with clinicopathologic factors in patients with colorectal cancer.

Authors:  Kisu Kim; Hyoun Wook Lee; Eun Hee Lee; Moon-Il Park; Jae Seok Lee; Mee-Seon Kim; Kyungeun Kim; Mee Sook Roh; Min Gyoung Pak; Ji Eun Oh; Kwang Min Kim; Jung Won Lee; Tae Gyu Kim; Hyun-Yeol Nam
Journal:  Int J Clin Exp Pathol       Date:  2019-03-01

6.  Pazopanib inhibits the activation of PDGFRβ-expressing astrocytes in the brain metastatic microenvironment of breast cancer cells.

Authors:  Brunilde Gril; Diane Palmieri; Yongzhen Qian; Talha Anwar; David J Liewehr; Seth M Steinberg; Zoraida Andreu; Daniel Masana; Paloma Fernández; Patricia S Steeg; Fernando Vidal-Vanaclocha
Journal:  Am J Pathol       Date:  2013-04-12       Impact factor: 4.307

Review 7.  Brain metastasis.

Authors:  Adrienne Boire; Priscilla K Brastianos; Livia Garzia; Manuel Valiente
Journal:  Nat Rev Cancer       Date:  2019-11-28       Impact factor: 60.716

8.  Heat shock protein-90 inhibitors increase MHC class I-related chain A and B ligand expression on multiple myeloma cells and their ability to trigger NK cell degranulation.

Authors:  Cinzia Fionda; Alessandra Soriani; Giulia Malgarini; Maria Luisa Iannitto; Angela Santoni; Marco Cippitelli
Journal:  J Immunol       Date:  2009-09-11       Impact factor: 5.422

9.  Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent.

Authors:  J G Supko; R L Hickman; M R Grever; L Malspeis
Journal:  Cancer Chemother Pharmacol       Date:  1995       Impact factor: 3.333

10.  HTSeq--a Python framework to work with high-throughput sequencing data.

Authors:  Simon Anders; Paul Theodor Pyl; Wolfgang Huber
Journal:  Bioinformatics       Date:  2014-09-25       Impact factor: 6.937
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  3 in total

1.  A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

Authors:  Lucía Zhu; Diana Retana; Pedro García-Gómez; Laura Álvaro-Espinosa; Neibla Priego; Mariam Masmudi-Martín; Natalia Yebra; Lauritz Miarka; Elena Hernández-Encinas; Carmen Blanco-Aparicio; Sonia Martínez; Cecilia Sobrino; Nuria Ajenjo; Maria-Jesus Artiga; Eva Ortega-Paino; Raúl Torres-Ruiz; Sandra Rodríguez-Perales; Riccardo Soffietti; Luca Bertero; Paola Cassoni; Tobias Weiss; Javier Muñoz; Juan Manuel Sepúlveda; Pedro González-León; Luis Jiménez-Roldán; Luis Miguel Moreno; Olga Esteban; Ángel Pérez-Núñez; Aurelio Hernández-Laín; Oscar Toldos; Yolanda Ruano; Lucía Alcázar; Guillermo Blasco; José Fernández-Alén; Eduardo Caleiras; Miguel Lafarga; Diego Megías; Osvaldo Graña-Castro; Carolina Nör; Michael D Taylor; Leonie S Young; Damir Varešlija; Nicola Cosgrove; Fergus J Couch; Lorena Cussó; Manuel Desco; Silvana Mouron; Miguel Quintela-Fandino; Michael Weller; Joaquín Pastor; Manuel Valiente
Journal:  EMBO Mol Med       Date:  2022-02-17       Impact factor: 12.137

Review 2.  Towards updated understanding of brain metastasis.

Authors:  Shuncong Wang; Yuanbo Feng; Lei Chen; Jie Yu; Chantal Van Ongeval; Guy Bormans; Yue Li; Yicheng Ni
Journal:  Am J Cancer Res       Date:  2022-09-15       Impact factor: 5.942

3.  Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Authors:  Cátia Monteiro; Lauritz Miarka; María Perea-García; Neibla Priego; Pedro García-Gómez; Laura Álvaro-Espinosa; Ana de Pablos-Aragoneses; Natalia Yebra; Diana Retana; Patricia Baena; Coral Fustero-Torre; Osvaldo Graña-Castro; Kevin Troulé; Eduardo Caleiras; Patricia Tezanos; Pablo Muela; Elisa Cintado; José Luis Trejo; Juan Manuel Sepúlveda; Pedro González-León; Luis Jiménez-Roldán; Luis Miguel Moreno; Olga Esteban; Ángel Pérez-Núñez; Aurelio Hernández-Lain; José Mazarico Gallego; Irene Ferrer; Rocío Suárez; Eva M Garrido-Martín; Luis Paz-Ares; Celine Dalmasso; Elizabeth Cohen-Jonathan Moyal; Aurore Siegfried; Aisling Hegarty; Stephen Keelan; Damir Varešlija; Leonie S Young; Malte Mohme; Yvonne Goy; Harriet Wikman; Jose Fernández-Alén; Guillermo Blasco; Lucía Alcázar; Clara Cabañuz; Sergei I Grivennikov; Andrada Ianus; Noam Shemesh; Claudia C Faria; Rebecca Lee; Paul Lorigan; Emilie Le Rhun; Michael Weller; Riccardo Soffietti; Luca Bertero; Umberto Ricardi; Joaquim Bosch-Barrera; Elia Sais; Eduard Teixidor; Alejandro Hernández-Martínez; Alfonso Calvo; Javier Aristu; Santiago M Martin; Alvaro Gonzalez; Omer Adler; Neta Erez; Manuel Valiente
Journal:  Nat Med       Date:  2022-04-11       Impact factor: 87.241
  3 in total

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