Cell death, senescence and cancer precision medicine. PI: Joan Montero

Presentation

Currently the group's work consists of developing new tools and discovering new therapies for the personalized treatment of cancer, collaborating with many international oncologists in several exciting translational medicine projects. My laboratory uses functional assays such as dynamic BH3 profiling for precision medicine aiming to improve the treatment of different types of cancer, both pediatric and adult.

KEYWORDS: Cancer, apoptosis, funcional assays, precision medicine, senescence

Joan Montero, PhD
Associate professor
jmontero@ub.edu

 

Clara Alcón, PhD
Postdoctoral researcher
clara.alcon@ub.edu

 

Marina Bantulà, PhD
Postdoctoral researcher
mbantulafonts@ub.edu

 

Albert Manzano, PhD
Postdoctoral researcher
amanzano@ub.edu

 

Fernando Martín
PhD student
fmartin@ibecbarcelona.eu
fmartisi8@alumnes.ub.edu

 

Paula Morales, PhD
Postdoctoral researcher
paula.morales@ub.edu

  • Functional precision medicine for different types of cancer, both pediatric and adult.
  • Identification of new therapies to avoid tumor resistance to treatments.
  • Development of new technologies for personalized cancer treatment.

Real-time tracking of apoptosis for precision medicine (RTAPREMED)

Principal Investigator: Juan Montero Boronat
Project reference: PDC2022-133583-I00
Funding entity: Ministerio de Ciencia, Innovación y Universidades
Name of the programme: Proj. de Prova de Concepte 2022
Period: 2022 – 2025

Centralization of pathological diagnosis and implementation of precision medicine strategies in sarcoma

Principal Investigator: Dr. de Álava, Dra. Romagosa, Dr. Serrano, Dra. Valverde and Dr. Montero
Project reference: Estudios Clínicos AECC 2022
Funding entity: Asociación Española Contra el Cáncer (AECC)
Affiliation entity: Universitat de Barcelona
Period: 01/10/2022 – 31/09/2025

Eliminación selectiva de células senescentes inducidas por terapia para evitar la recaída del cáncer de pulmón

Principal Investigator: Joan Montero Boronat
Project reference: PID2021-128644OB-I00
Funding entity: MInisterio de Ciencia e Innovación, Proy. de Generación del Conocimiento 2021
Affiliation entity: Universitat de Barcelona
Period: 01/09/2022 – 31/08/2025

Integrative analysis in dynamic resistance in non-responding relapsed pediàtric acute lymphoblastic leukemia patients

Principal Investigator: Joan Montero Boronat (in collaboration with the Berlin Charité)
Project reference: DJCLS 19R/2022
Funding entity: José Carreras Leukämie-Stiftung
Affiliation entity: Universitat de Barcelona
Period: 01/09/2022 – 31/08/2025

Personalización Del Tratamiento De La Leucemia Linfoblástica Aguda Pediátrica Mediante Dynamic BH3 Profiling

Principal Investigator: Joan Montero Boronat
Project reference: Non-competitive research project
Funding entity: Asociación Pablo Ugarte
Affiliation entity: Universitat de Barcelona
Period: 01/05/2022 :N/A

Cell Compartments: trafficking and signaling in health and disease

Principal Investigator: Neus Agell, Albert Pol, Carles Enrich, Joan Montero
Project reference: 2021SGR00284 (SGR-Cat 2021)
Funding entity: AGAUR
Affiliation entity: Universitat de Barcelona
Period: 2022 - 2024

Functional Tumor Cell Response to Neoadjuvant Chemotherapy in Soft Tissue Sarcomas

Principal Investigator: Joan Montero Boronat
Project reference: V Three-year scholarship
Funding entity: Fundación Mari Paz Jiménez Casado
Affiliation entity: Universitat de Barcelona
Period: 15/12/2021 – 31/12/2024

Microfluidic cell-based functional assay development for personalized cancer treatment (PREMED)

Principal Investigator Joan Montero Boronat
Project reference: RTI2018-094533-A-I00
Funding entity: Ministerio de Ciencia, Innovación y Universidades
Affiliation entity: Universitat de Barcelona
Period: 01/01/2019 – 31/08/2022 (completed)

Ramon y Cajal award - Personalized therapy for cancer using microfluidics systems

Principal Investigator: Joan Montero Boronat
Project reference:: RYC-2015-18357
Funding entity:: Ministerio de Ciencia, Innovación y Universidades
Affiliation entity: Universitat de Barcelona
Period: 01/09/2017 – 31/08/2022 (completed)

Personalizing pediatric cancer treatment

Principal Investigator: Joan Montero Boronat
Project reference: Non-competitive research project
Funding entity: Fundació FERO
Affiliation entity: Universitat de Barcelona
Period: 01/01/2018– 31/12/2018 (completed)

Personalizing pediatric cancer treatment with kinome analyses, cell-based functional assays and microfluidics

Principal Investigator: Joan Montero Boronat and Josep Samitier Martí
Project reference: Non-competitive research project
Funding entity: Fundació CELLEX
Affiliation entity: Universitat de Barcelona
Period: 01/09/2017 – 31/08/2020 (completed)

Personalizing melanoma treatment using Dynamic BH3 Profiling

Principal Investigator: Joan Montero Boronat and Anthony Letai
Project reference: D2015-037
Funding entity: Stand Up to Cancer / The V Foundation
Affiliation entity: Universitat de Barcelona
Period: 01/02/2016 – 01/02/2020 (completed)

Real-time tracking of apoptosis:

Type: PCT application WO202413236A1
Inventors: Juan Montero, Albert Manzano, Josep Samitier, Javier Ramón, M. Alejandra Ortega.
International Publication
Date: 18/01/2024

Co-inventor of the New predictive biomarker for therapy response called dynamic BH3 profiling (DBP) initially developed at the Dana-Farber Cancer Institute (DFCI):

Title: Dynamic BH3 Profiling
Authors: Anthony Letai, Juan Montero Boronat and Jeremy Ryan
Sol./Country: US PCT/US2013/060707
Priority date: 19/09/2012
Owner entity: Dana-Farber Cancer Institute, Inc.

For more information for PI publications click in the link:
ORCID ID: 0000-0002-9192-4836

 

 

V Ruiz de Porras, A Bernat-Peguera, C Alcon, F Laguia, ... Dual inhibition of MEK and PI3Kβ/δ-a potential therapeutic strategy in PTEN-wild-type docetaxel-resistant metastatic prostate cancer.  Front Pharmacol. 2024 Jan 22:15: 1331648. doi: 10.3389/ fphar.2024.1331648. eCollection 2024. PMID: 38318136

A Manzano-Muñoz, J Yeste, MA Ortega, J Samitier, J Ramón-Azcón, ... A New Microfluidic Device to Facilitate Functional Precision Medicine Assays. Methods Mol Biol. 2024:2748: 99-108. doi: 10.1007 / 978-1-0716-3593-3_8. PMID: 38070110

E Almici, M Arshakyan, JL Carrasco, A Martínez, J Ramírez, AB Enguita, ... Quantitative Image Analysis of Fibrillar Collagens Reveals Novel Diagnostic and Prognostic Biomarkers and Histotype-Dependent Aberrant Mechanobiology in Lung Cancer. Modern Pathology Volume 36, Issue 7, July 2023, 100155. https://doi.org/10.1016/j.modpat.2023.100155

F Selt, R Sigaud, G Valinciute, P Sievers, J Zaman, C Alcon, S Schmid, ... BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma. Neuro-Oncology, Volume 25, Issue 4, April 2023, Pages 735–747, https://doi.org/10.1093/neuonc/noac199

P Velasco, F Bautista, A Rubio, Y Aguilar, S Rives, JL Dapena, A Pérez, ... The relapsed acute lymphoblastic leukemia network (ReALLNet): a multidisciplinary project from the spanish society of pediatric hematology and oncology (SEHOP). Front Pediatr 2023; 11: 1269560. Published online 2023 Sep 20. doi: 10.3389/ fped.2023.1269560. PMC10547895

Z Inde, J Montero, K Sarosiek, Mitochondria in Cell Death Regulation. Academic Press 2023/01/01. pg. 1525-164

Manzano-Muñoz A, Yeste J, Ortega MA, Martín F, López A, Rosell J, Castro S, Serrano C, Samitier J, Ramón-Azcón J, Montero J. Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy. NPJ Precis Oncol. 2022 Dec 1;6(1):90. doi: 10.1038/s41698-022-00333-0. PMID: 36456699

Selt F, Sigaud R, Valinciute G, Sievers P, Zaman J, Alcon C, Schmid S, Peterziel H, Tsai JW, Guiho R, Martínez-Barbera JP, Pusch S, Deng J, Zhai Y, van Tilburg CM, Schuhman MU, Damaty AEL, Bandopadhayay P, Herold-Mende C, von Deimling A, Pfister SM, Montero J, Capper D, Oehme I, Sahm F, Jones DTW, Witt O, Milde T. BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma. Neuro Oncol. 2022 Aug 17:noac199. doi: 10.1093/neuonc/noac199. PMID: 35977048.

Montero J., Haq R. Adapted to Survive: Targeting Cancer Cells with BH3 Mimetics. Cancer Discov. 2022 May 2;12(5): 1217-1232.  doi: 10.1158/ 2159-8290.CD-21-1334. PMID: 35491624

Alcon C, Martín F, Prada E, Mora J, Soriano A, Guillén G, Gallego S, Roma J, Samitier J, Villanueva A, Montero J. MEK and MCL-1 sequential inhibition synergize to enhance rhabdomyosarcoma treatment. Cell Death Discov. 2022 Apr 7; 8(1):172. doi: 10.1038/ s41420-022-00959-w. PMID: 35393436

Almici E, Chiappini V, López-Márquez A, Badosa C, Blázquez B, Caballero D, Montero J, Natera-de Benito D, Nascimento A, Roldán M, Lagunas A, Jiménez-Mallebrera C, Samitier J. Personalized in vitro Extracellular Matrix Models of Collagen VI-Related Muscular Dystrophies.

Schroeder B, Vander Steen T, Espinoza I, Venkatapoorna CMK, Hu Z, Silva FM, Regan K, Cuyàs E, Meng XW, Verdura S, Arbusà A, Schneider PA, Flatten KS, Kemble G, Montero J, Kaufmann SH, Menendez JA, Lupu R. Fatty acid synthase (FASN) regulates the mitochondrial priming of cancer cells. Cell Death Dis. 2021 Oct 21; 12(11):977. doi: 10.1038/ s41419-021-04262-x. PMID: 34675185

Gómez Tejeda Zañudo J, Mao P, Alcon C, Kowalski K, Johnson GN, Xu G, Baselga J, Scaltriti M, Letai A, Montero J, Albert R, Wagle N. Cell Line-Specific Network Models of ER+ Breast Cancer Identify Potential PI3Kα Inhibitor Resistance Mechanisms and Drug Combinations. Cancer Res. 2021 Sep 1;81(17): 4603-4617. doi: 10.1158/ 0008-5472.CAN-21-1208. Epub 2021 Jul 13. PMID: 34257082

Alcon C, Gómez Tejeda Zañudo J, Albert R, Wagle N, Scaltriti M, Letai A, Samitier J, Montero J. ER+ Breast Cancer Strongly Depends on MCL-1 and BCL-xL Anti-Apoptotic Proteins. Cells. 2021 Jul 2;10(7): 1659. doi: 10.3390/ cells10071659. PMID: 34359829

Manzano-Muñoz A, Alcon C, Menéndez P, Ramírez M, Seyfried F, Debatin KM, Meyer LH, Samitier J, Montero J. MCL-1 Inhibition Overcomes Anti-apoptotic Adaptation to Targeted Therapies in B-Cell Precursor Acute Lymphoblastic Leukemia. Front Cell Dev Biol. 2021 Sep 9; 9:695225. doi: 10.3389/ fcell.2021.695225. eCollection 2021. PMID: 34568318

Watt AC, Cejas P, DeCristo MJ, Metzger-Filho O, Lam EYN, Qiu X, BrinJones H, Kesten N, Coulson R, Font-Tello A, Lim K, Vadhi R, Daniels VW, Montero J, Taing L, Meyer CA, Gilan O, Bell CC, Korthauer KD, Giambartolomei C, Pasaniuc B, Seo JH, Freedman ML, Ma C, Ellis MJ, Krop I, Winer E, Letai A, Brown M, Dawson MA, Long HW, Zhao JJ, Goel S.CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity. Nat Cancer. 2021 Jan; 2(1):34-48. doi: 10.1038/ s43018-020-00135-y. Epub 2020 Nov 9. PMID: 33997789

Serrat N, Guerrero-Hernández M, Matas-Céspedes A, Yahiaoui A, Valero JG, Nadeu F, Clot G, Di Re M, Corbera-Bellalta M, Magnano L, Rivas-Delgado A, Enjuanes A, Beà S, Cid MC, Campo E, Montero J, Hodson DJ, López-Guillermo A, Colomer D, Tannheimer S, Pérez-Galán P. PI3Kδ inhibition reshapes follicular lymphoma-immune microenvironment cross talk and unleashes the activity of venetoclax. Blood Adv. 2020 Sep 8; 4(17):4217-4231. doi: 10.1182/ bloodadvances. 2020001584. PMID: 32898249

Alcon C, Manzano-Muñoz A, Prada E, Mora J, Soriano A, Guillén G, Gallego S, Roma J, Samitier J, Villanueva A, Montero J. Sequential combinations of chemotherapeutic agents with BH3 mimetics to treat rhabdomyosarcoma and avoid resistance. Cell Death Dis. 2020 Aug 15; 11(8):634. doi: 10.1038/ s41419-020-02887-y. PMID: 32801295

Alcon C, Manzano-Muñoz A and Montero J. A new CDK9 inhibitor on the block to treat hematological malignancies. Clin Cancer Res. 2020 Feb 15; 26(4):761-763. doi: 10.1158/ 1078-0432.CCR-19-3670. Epub 2019 Dec 16. PMID: 31843752

Montero J, Gstalder C, Kim DJ, Sadowicz D, Miles W,[…], Fisher DE, Haq R. Destabilization of NOXA mRNA as a common resistance mechanism to targeted therapies. Nat Commun. 2019 Nov 14;10(1): 5157. doi: 10.1038/ s41467-019-12477-y. PMID: 31727958

Stover EH, Baco MB, Cohen O, Li YY, Christie EL, Bagul M, Goodale A, Lee Y, Pantel S, Rees MG, Wei G, Presser AG, Gelbard MK, Zhang W, Zervantonakis IK, Bhola PD, Ryan J, Guerriero JL, Montero J, Liang FJ, Cherniack AD, Piccioni F, Matulonis UA, Bowtell DDL, Sarosiek KA, Letai A, Garraway LA, Johannessen CM, Meyerson M. Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer. Mol Cancer Res. 2019 Nov; 17(11):2281-2293. doi: 10.1158/ 1541-7786. MCR-18-1243. Epub 2019 Aug 28. PMID: 31462500

Togami K, Pastika T, Stephansky J, Ghandi M, Christie AL, Jones KL, Johnson CA, Lindsay RW, Brooks CL, Letai A, Craig JW, Pozdnyakova O, Weinstock DM, Montero J, Aster JC, Johannessen CM, Lane AA. DNA methyltransferase inhibition overcomes diphthamide pathway deficiencies underlying CD123-targeted treatment resistance. J Clin Invest. 2019 Nov 1; 129(11):5005-5019. doi: 10.1172/ JCI128571. PMID: 31437130

Park DE, Cheng J, Berrios C, Montero J, Cortés-Cros M, Ferretti S, Arora R, Tillgren ML, Gokhale PC, DeCaprio JA. Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response. Proc Natl Acad Sci U S A. 2019 Jan 15; 116(3): 1027-1032. doi: 10.1073/ pnas.1818798116. Epub 2018 Dec 31. PMID: 30598450

Baulies A, Montero J, Matías N, [...], Kaplowitz N, Garcia-Ruiz C, Fernández-Checa JC. The 2-oxoglutarate carrier promotes liver cancer by sustaining mitochondrial GSH despite cholesterol loading. Redox Biol. 2018 Apr; 14:164-177. doi: 10.1016/ j.redox.2017.08.022. Epub 2017 Sep 14. PMID: 28942194

Montero J, Letai A. Why do BCL-2 inhibitors work and where should we use them in the clinic? Cell Death Differ. 2018 Jan; 25(1):56-64. doi: 10.1038/ cdd.2017.183. Epub 2017 Oct 27. PMID: 29077093

Lagares D, Santos A, Grasberger PE, Liu F, Probst CK, Rahimi RA, Sakai N, Kuehl T, Ryan J, Bhola P, Montero J, Kapoor M, Baron M, Varelas X, Tschumperlin DJ, Letai A, Tager AM. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Sci Transl Med. 2017 Dec 13;9(420): eaal3765. doi: 10.1126/ scitranslmed.aal3765. PMID: 29237758

Pallis M, Burrows F, Ryan J, Grundy M, Seedhouse C, Abdul-Aziz A, Montero J, Letai A, Russell N. Complementary dynamic BH3 profiles predict co-operativity between the multi-kinase inhibitor TG02 and the BH3 mimetic ABT-199 in acute myeloid leukaemia cells. Oncotarget. 2017 Mar 7; 8(10): 16220-16232. doi: 10.18632/ oncotarget.8742. PMID: 27092880

Montero J*, Stephansky J*, Cai T, Griffin GK, […], Konopleva M, Pemmaraju N, Letai A, Lane AA. Blastic plasmacytoid dendritic cell neoplasm is dependent on BCL-2 and sensitive to venetoclax. Cancer Discov. 2017 Feb;7(2): 156-164. doi: 10.1158/ 2159-8290.CD-16-0999. Epub 2016 Dec 16. PMID: 27986708

Ryan J, Montero J, Rocco J, Letai A. iBH3: simple, fixable BH3 profiling to determine apoptotic priming in primary tissue by flow cytometry. Biol Chem. 2016 Jul 1; 397(7): 671-8. doi: 10.1515/ hsz-2016-0107. PMID: 26910743

Montero J, Letai A. Dynamic BH3 profiling-poking cancer cells with a stick. Mol Cell Oncol. 2016 Mar 10;3(3): e1040144. doi: 10.1080/ 23723556.2015.1040144. eCollection 2016 May. PMID: 27314085

Townsend EC, Murakami MA, Christodoulou A, Christie AL, Köster J, DeSouza TA, Morgan EA, Kallgren SP, Liu H, Wu SC, Plana O, Montero J, [...], Weinstock DM. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 Apr 11; 29(4): 574-586. doi: 10.1016/ j.ccell.2016.03.008. PMID: 27070704

Etchin J, Montero J, [...], Kung AL, Wang JC, Letai A, Look AT. Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice. Leukemia. 2016 Jan; 30(1): 190-9. doi: 10.1038/ leu.2015.194. Epub 2015 Jul 23. PMID: 26202935

Wu S*, Li LS*, Kopp N*, Montero J, Chapuy B, […], Gaul C, Weinstock DM. Activity of the Type II JAK2 Inhibitor CHZ868 in B Cell Acute Lymphoblastic Leukemia. Cancer Cell. 2015 Jul 13; 28(1): 29-41. doi: 10.1016/ j.ccell.2015.06.005. PMID: 26175414

Montero J, Sarosiek KA, DeAngelo JD, Ryan J, Ercan D, Piao H, Horowitz NS, Berkowitz RS, Matulonis U, Jänne PA, Amrein PC, Drapkin R, Letai A. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell. 2015 Feb 26; 160(5): 977-989. doi: 10.1016/ j.cell.2015.01.042. PMID: 25723171

 

Books and book chapters:

Book title: Encyclopedia of Cell Biology, Second Edition
Author/s (by order of signature): Inde Z, Montero J, Sarosiek K
Chapter Title (if applicable): Mitochondria in Cell Death Regulation
Year: 2022
Pages (start-end):
Editorial: Elsevier
ISBN: 9780128216187
DOI (if applicable):

Book title: Methods in cell biology: Cell-derived Matrices
Author/s (by order of signature): Almici E, Caballero D#, Montero J, Samitier J
Chapter Title (if applicable): Engineering cell-derived matrices with controlled 3d architectures for pathophysiological studies, 2020, issue 1
Year: 2020
Pages (start-end): Volume 156
Editorial: Elsevier
ISBN: 9780128201725
DOI (if applicable): https://doi.org/10.1016/bs.mcb.2019.11.022

Book title: Biomaterials for 3D Tumor Modeling
Author/s (by order of signature): Almici E, Caballero D#, Montero J, Samitier J
Chapter Title (if applicable): 3D neuroblastoma in vitro models using engineered cell-derived matrices
Year: 2020
Pages (start-end): 107-130
Editorial: Elsevier
ISBN: 9780128181287
Dipòsit legal (si escau):
DOI (if applicable): https://doi.org/10.1016/B978-0-12-818128-7.00005-8

  • Offers from the University of Barcelona:

Work UB

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