Models of Cancer Therapies Group

PRECLINICAL & TRANSLATIONAL RESEARCH

Our group focuses on the pleiotropic and ubiquitous Myc oncoprotein, whose deregulation is implicated in almost all human cancers. The technical challenges of targeting nuclear transcription factors such as Myc –and the concern regarding potential side effects– had until recently precluded any preclinical validation of Myc inhibition as a possible therapeutic strategy.

Over the past few years, we have demonstrated in several mouse models that MYC inhibition has a dramatic therapeutic impact across several tumor types, with very mild and reversible side effects in normal tissue.

Encouraged by our results in mice, we are now interested in developing viable, non-toxic pharmacological options for MYC targeting in the clinic. To do so, we created a spin-off company, Peptomyc S.L., for the development of MYC-inhibiting peptides for cancer therapy. Our laboratory, in partnership with Peptomyc, is currently validating our novel approach against notoriously difficult-to-treat cancers that are resistant to standard treatments and in dire need of new therapeutic avenues (i.e., KRAS-driven Non-Small Cell Lung Cancer, glioblastoma, and metastatic triple negative breast cancer).

The first Omomyc-derived compound, OMO-103, successfully completed the phase I part of the Phase I/IIa clinical trial in October 2022. The trial was sponsored by Peptomyc and performed in 3 Spanish hospitals including the Vall d’Hebron University Hospital – HUVH (Vall d’Hebron Barcelona Hospital Campus). Results of the trial were presented at the 34^th EORTC-NCI-AACR Symposium held in Barcelona, 26-28 October 2022. Notably, this is the first direct MYC inhibitor to have ever reached this stage of clinical development.

Our group has continued to contribute to cancer research in general and, more specifically, as a leader in the MYC field, by (co) authoring articles and reviews, exploring new aspects of MYC biology in different pathologies and summarizing efforts to develop a clinically viable MYC inhibitor.

Laura Soucek

Group Leader

Biosketch

Jonathan R. Whitfield

Senior Researcher

Biosketch

Research Lines

Preclinically validate novel therapeutic strategies against MYC in breast, brain, lung, neuroblastoma, melanoma, and colorectal cancer.
Validate anti-MYC Omomyc-based cell penetrating mini-proteins for cancer therapy.
Identify and validate biomarkers of response to MYC inhibition.
Define the role of MYC in promoting cancer immune evasion and test the efficacy of MYC inhibitors and IO combination therapies in cancer treatment.
Develop potent combinations of Omomyc with current therapeutics, including PARP inhibitors (PARPi) in the context of DNA Damage Response (DDR) deficient tumors.
Investigate how the MYC network functions in Max-defective gastrointestinal stromal tumors (GISTs) and Small-Cell Lung Cancer (SCLC) to define actionable targets to tackle these unmet clinical needs.

Figure: Adapted from Massó-Vallés and Soucek, 2020: Representation of the crystal structure of the MYC/MAX dimer (1NKP, left) and Omomyc/Omomyc dimer (5I50, right) bHLHZ bound to DNA.

Team

Group Leader

Laura Soucek

Senior Researcher

Jonathan R. Whitfield

Research Associate

Mariano F. Zacarías-Fluck

Post-Doctoral Fellows

Ana Lopez Garza

Technicians

Judit Grueso

Erika Serrano del Pozo

Romina Mariel Rodriguez

Manrique Jose Valdez-Bango

PhD Students

Daniel Capitán Leo

Fabio Giuntini

Íñigo González-Larreategui

Publications

Most relevant scientific publications

Martínez-Martín S, Beaulieu ME, Soucek L. Targeting MYC-driven lymphoma: lessons learned and future directions. Cancer Drug Resist. 2023 Apr 12;6(2):205-222.
Zacarías-Fluck MF, Massó-Vallés D, Giuntini F, González-Larreategui Í, Kaur J, Casacuberta-Serra S, Jauset T, Martínez-Martín S, Martín-Fernández G, Serrano Del Pozo E, Foradada L, Grueso J, Nonell L, Beaulieu ME, Whitfield JR, Soucek L. Reducing MYC’s transcriptional footprint unveils a good prognostic gene signature in melanoma. Genes Dev. 2023 Apr 1;37(7-8):303-320.
Beaulieu ME, Martínez-Martín S, Kaur J, Castillo Cano V, Massó-Vallés D, Foradada Felip L, López-Estévez S, Serrano Del Pozo E, Thabussot H, Soucek L. Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue. Cancers (Basel). 2023 Jan 29;15(3):826.
Casacuberta-Serra S, Gonzalez-Larreategui I, Soucek L. eIF4A dependency: the hidden key to unlock KRAS mutant non-small cell lung cancer’s vulnerability. Transl Lung Cancer Res. 2023 Dec 26;12(12):2570-2575.
Kaur, J, Soucek, L. Going for a “KDIP” in colorectal cancer treatment. Clin Transl Disc. 2022; 2:e108.
Massó-Vallés D, Beaulieu ME, Jauset T, Giuntini F, Zacarías-Fluck MF, Foradada L, Martínez-Martín S, Serrano E, Martín-Fernández G, Casacuberta-Serra S, Castillo Cano V, Kaur J, López-Estévez S, Morcillo MÁ, Alzrigat M, Mahmoud L, Luque-García A, Escorihuela M, Guzman M, Arribas J, Serra V, Larsson LG, Whitfield JR, Soucek L. MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding. Cancer Res Commun. 2022 Feb 21;2(2):110-130.
Whitfield JR, Soucek L. The long journey to bring a Myc inhibitor to the clinic. J Cell Biol. 2021 Aug 2;220(8):e202103090.
Zacarías-Fluck MF, Jauset T, Martínez-Martín S, Kaur J, Casacuberta-Serra S, Massó-Vallés D, Serrano Del Pozo E, Martín-Fernández G, González-Larreategui Í, López-Estévez S, Brown-Swigart L, Beaulieu ME, Whitfield JR, Madan B, Virshup DM, Evan GI, Soucek L. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets. Life Sci Alliance. 2021 Mar 2;4(5):e201900490. Print 2021 May.
Martínez-Martín S, Soucek L. MYC inhibitors in multiple myeloma. Cancer Drug Resist 2021;4:842-65.10.20517/cdr.2021.55.
Whitfield J, Soucek L. An “-omycs” Toolbox to Work with MYC. Methods Mol Biol. 2021;2318:1-11
Beaulieu ME, Castillo F, Soucek L. Structural and Biophysical Insights into the Function of the Intrinsically Disordered Myc Oncoprotein. Cells. 2020 Apr22;9(4):1038.
Massó-Vallés D, Soucek L. Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc. Cells. 2020 Apr 4;9(4):883. doi: 10.3390/ cells9040883.PMID: 32260326
Beaulieu ME, Jauset T, Massó-Vallés D, Martínez-Martín S, Rahl P, Maltais L, Zacarias-Fluck MF, Casacuberta-Serra S, Serrano del Pozo E, Fiore C, Foradada L, Castillo Cano V, Guenther M, Romero Sanz E, Oteo M, Tremblay C, Martín G, Letourneau D, Montagne M, Morcillo Alonso MA, Whitfield JR, Lavigne P, Soucek L. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-Myc therapy. Sci Trans Med. 2019 Mar 20;11(484).
Beaulieu ME, Soucek L. Finding MYCure. Mol Cell Oncol. 2019 Jun 20;6(5):e1618178.
Pesarrodona M, Jauset T, Díaz-Riascos ZV, Sánchez-Chardi A, Beaulieu ME, Seras-Franzoso J, Sánchez-García L, Baltà-Foix, Sandra Mancilla R, Fernández Y, Rinas U, Schwartz Jr S, Soucek L, Villaverde A, Abasolo I, Vázquez E. Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies. Adv Sci. 2019 Jul 24.
Whitfield JR, Soucek L. Editorial Overview: Peptides in Cancer. Curr Opin Pharmacol. 2019 Jun 27. pii: S1471-4892(19)30045-1.
Beaulieu ME, Jauset T, Massó-Vallés D, Martínez-Martín S, Rahl P, Maltais L, Zacarias-Fluck MF, Casacuberta-Serra S, Serrano Del Pozo E, Fiore C, Foradada L, Cano VC, Sánchez-Hervás M, Guenther M, Romero Sanz E, Oteo M, Tremblay C, Martín G, Letourneau D, Montagne M, Morcillo Alonso MÁ, Whitfield JR, Lavigne P, Soucek L. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-MYC therapy. Sci Transl Med. 2019 Mar 20;11(484). Link to Abstract
Jauset T, Massó-Vallés D, Martínez-Martín S, Beaulieu ME, Foradada L, Fiorentino FP, Yokota J, Haendler B, Siegel S, Whitfield JR, Soucek L. BET inhibition is an effective approach against KRAS-driven PDAC and NSCLC. Oncotarget. 2018 Apr 10;9(27):18734-18746.
Dang C, Reddy EP, Shokat K, and Soucek L. Drugging the ‘undruggable’ cancer targets. Nat Rev Cancer. 2017 Aug;17(8):502-508.
Pedersen K, Bilal F, Bernadó Morales C, Salcedo MT, Macarulla T, Massó-Vallés D, Mohan V, Vivanco A, Carreras MJ, Serres X, Abu-Suboh M, Balsells J, Allende E, Sagi I, Soucek L, Tabernero J, Arribas J. Pancreatic cancer heterogeneity and response to Mek inhibition. Oncogene. 2017 Oct 5;36(40):5639-5647.
Whitfield JR, Beaulieu ME, Soucek L. Strategies to inhibit Myc and their clinical applicability. Front Cell Dev Biol. 2017 Feb 23;5:10. eCollection 2017.
Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin AV, Bruna A, Budinská E, Caldas C, Chang DK, Clarke RB, Clevers H, Coukos G, Dangles-Marie V, Eckhardt SG, Gonzalez-Suarez E, Hermans E, Hidalgo M, Jarzabek MA, de Jong S, Jonkers J, Kemper K, Lanfrancone L, Mælandsmo GM, Marangoni E, Marine JC, Medico E, Norum JH, Palmer HG, Peeper DS, Pelicci PG, Piris-Gimenez A, Roman-Roman S, Rueda OM, Seoane J, Serra V, Soucek L, Vanhecke D, Villanueva A, Vinolo E, Bertotti A, Trusolino L.. Interrogating open issues in cancer precision medicine using Patient-Derived Xenograft Models. Nat Rev Cancer. 2017 Apr;17(4):254-268.
Massó-Vallés D, Jauset T, Soucek L. Ibrutinib repurposing: from B cell malignancies to solid tumors. Oncoscience. 2016 Jun 10;3(5-6):147-8.
Fiorentino FP, Tokgün E, Solé-Sánchez S, Giampaolo S, Tokgün O, Jauset T, Kohno T, Perucho M, Soucek L, Yokota J. Growth Suppression by MYC Inhibition in Small Cell Lung Cancer Cells with TP53 and RB1 Inactivation. Oncotarget. 2016 May 24;7(21):31014-28.
Daniel Massó-Vallés, Toni Jauset and Laura Soucek. Ibrutinib repurposing: from B cell malignancies to solid tumors. Oncoscience. Onlibe Advanced Publication DOI: 10.18632/oncoscience.310. Editorial.
Francesco Paolo Fiorentino, Elvan Tokgün, Sònia Solé-Sánchez, Sabrina Giampaolo, Onur Tokgün, Toni Jauset, Takashi Kohno, Manuel Perucho, Laura Soucek, Jun Yokota. Growth Suppression by MYC Inhibition in Small Cell Lung Cancer Cells with TP53 and RB1 Inactivation. Oncotarget. 2016 Apr 18. doi: 10.18632/oncotarget.8826. [Epub ahead of print] Article.
Stephanie C. Casey, Monica Vaccari, Fahd Al-Mulla, Rabeah Al-Temaimi, Amedeo Amedei, Mary Helen Barcellos-Hoff, Dustin Brown, Marion Chapellier, […], Sandra Ryeom, Hosni K. Salem, Ivana Scovassi, Neetu Singh, Laura Soucek, Louis Vermeulen, Jonathan R. Whitfield, Jordan Woodrick, Annamaria Colacci, William H. Bisson, and Dean W. Felsher. Assessing the Carcinogenic Potential of Environmental Chemicals: The Tumor Microenvironment. Carcinogenesis. 2015 Jun;36 Suppl 1:S160-83. Review.
Daniel Massó-Vallés, Toni Jauset, Erika Serrano, Nicole M. Sodir, Kim Pedersen, Nesrine I. Affara, Jonathan R. Whitfield, Marie-Eve Beaulieu, Gerard I. Evan, Laurence Elias, Joaquín Arribas and Laura Soucek. Ibrutinib exerts potent anti-fibrotic and anti-tumor activity in mouse transgenic and patient derived xenograft models of pancreatic adenocarcinoma. Cancer Res. 2015 Apr 15; 75(8): 1675-1681. Article.
Daniela Annibali, Jonathan R Whitfield, Emilia Favuzzi, Toni Jauset, Erika Serrano, Isabel Cuartas, Sara Redondo-Campos, Gerard Folch, Alba Gonzàlez-Juncà, Nicole M Sodir, Daniel Massó-Vallés, Marie-Eve Beaulieu, Lamorna B Swigart, Margaret M Mc Gee, Maria Patrizia Somma, Sergio Nasi, , Joan Seoane, Gerard I Evan, and Laura Soucek. Myc Inhibition as a Therapeutic Strategy Against Glioma: a Role for Myc in Proficient Mitosis. Nat Communications. 2014 Aug 18;5:4632. Article.
Laura Soucek, Jonathan R. Whitfield, Nicole M. Sodir, Daniel Massó-Vallés, Erika Serrano, Anthony N. Karnezis, Lamorna Brown Swigart and Gerard I. Evan. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev. 2013 Mar 1;27(5):504-13. Article.
Whitfield J, Soucek L. Tumor microenvironment: becoming sick of Myc. Cell Mol Life Sci. 2012, 69(6), 931-934. Review.
Nicole M Sodir, Lamorna Brown Swigart, Anthony N Karnezis, Douglas Hanahan, Gerard Evan and Laura Soucek. Endogenous Myc maintains the tumor microenvironment. Genes Dev. 2011 May 1;25(9):907-16. Epub 2011 Apr 8. Article.
Andrew Finch*, Laura Soucek*, Melissa Junttila, Lamorna Brown Swigart and Gerard I. Evan. Acute over-expression of Myc in intestinal epithelium recapitulates some but not all the changes elicited by Wnt/β-catenin pathway activation. Mol Cell Biol. 2009 Oct;29(19):5306-15. Epub 2009 Jul 27. Article. *Joint first authors
Laura Soucek, Jonathan Whitfield, Carla P. Martins, Andrew J. Finch, Nicole M. Sodir, Lamorna Brown Swigart, Sergio Nasi and Gerard I. Evan. Modelling Myc inhibition as a cancer therapy. Nature. 2008 Oct 2;455(7213):679-83. Epub 2008 Aug 17. Article.
Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors. Nat Med. 2007 Oct;13(10):1211-8. Epub 2007 Sep 30. Article.
Maria A. Christophorou, Dionisio Martin-Zanca, Laura Soucek, Elizabeth Lawlor, Emmy Verschuren, Lamorna Brown-Swigart and Gerard I. Evan. Temporal dissection of p53 function in vitro and in vivo.Nature Genetics. 2005 Jul;37(7):718-26. Article.
Laura Soucek, Sergio Nasi, and Gerard Evan. Omomyc expression in skin prevents Myc-induced papillomatosis. Cell Death Differ. 2004 Sep;11(9):1038-45. Article.
Laura Soucek and Gerard Evan. Myc – is this the oncogene from Hell?. Cancer Cell. 2002 June; 1(5): 406-408. Review.
Laura Soucek, Richard Jucker, Laura Panacchia, Ruggero Ricordy, Franco Tatò, and Sergio Nasi. Omomyc, a Potential Myc Dominant Negative, Enhances Myc-induced Apoptosis. Cancer Res. 2002; 62: 3507-3510. Article.
Soucek L., Citterich M.H., Sacco A., Jucker R., Cesareni G. and Nasi S. Design and properties of a Myc derivative that efficiently homodimerizes. Oncogene. 1998, 17(19): 2463-2472. Article.

All publications

Martínez-Martín S, Beaulieu ME, Soucek L. Targeting MYC-driven lymphoma: lessons learned and future directions. Cancer Drug Resist. 2023 Apr 12;6(2):205-222.
Zacarías-Fluck MF, Massó-Vallés D, Giuntini F, González-Larreategui Í, Kaur J, Casacuberta-Serra S, Jauset T, Martínez-Martín S, Martín-Fernández G, Serrano Del Pozo E, Foradada L, Grueso J, Nonell L, Beaulieu ME, Whitfield JR, Soucek L. Reducing MYC’s transcriptional footprint unveils a good prognostic gene signature in melanoma. Genes Dev. 2023 Apr 1;37(7-8):303-320.
Beaulieu ME, Martínez-Martín S, Kaur J, Castillo Cano V, Massó-Vallés D, Foradada Felip L, López-Estévez S, Serrano Del Pozo E, Thabussot H, Soucek L. Pharmacokinetic Analysis of Omomyc Shows Lasting Structural Integrity and Long Terminal Half-Life in Tumor Tissue. Cancers (Basel). 2023 Jan 29;15(3):826.
Casacuberta-Serra S, Gonzalez-Larreategui I, Soucek L. eIF4A dependency: the hidden key to unlock KRAS mutant non-small cell lung cancer’s vulnerability. Transl Lung Cancer Res. 2023 Dec 26;12(12):2570-2575.
Kaur, J, Soucek, L. Going for a “KDIP” in colorectal cancer treatment. Clin Transl Disc. 2022; 2:e108.
Massó-Vallés D, Beaulieu ME, Jauset T, Giuntini F, Zacarías-Fluck MF, Foradada L, Martínez-Martín S, Serrano E, Martín-Fernández G, Casacuberta-Serra S, Castillo Cano V, Kaur J, López-Estévez S, Morcillo MÁ, Alzrigat M, Mahmoud L, Luque-García A, Escorihuela M, Guzman M, Arribas J, Serra V, Larsson LG, Whitfield JR, Soucek L. MYC Inhibition Halts Metastatic Breast Cancer Progression by Blocking Growth, Invasion, and Seeding. Cancer Res Commun. 2022 Feb 21;2(2):110-130.
Pighi C, Cheong TC, Compagno M, Patrucco E, Arigoni M, Olivero M, Wang Q, López C, Bernhart SH, Grande BM, Poggio T, Langellotto F, Bonello L, Dall’Olio R, Martínez-Martín S, Molinaro L, Francia di Celle P, Whitfield JR, Soucek L, Voena C, Calogero RA, Morin RD, Staudt LM, Siebert R, Zamò A, Chiarle R. Frequent mutations of FBXO11 highlight BCL6 as a therapeutic target in Burkitt lymphoma. Blood Adv. 2021 Dec 14;5(23):5239-5257. doi: 10.1182/bloodadvances.2021005682.
Martínez-Martín S, Soucek L. MYC inhibitors in multiple myeloma. Cancer Drug Resist2021;4:842-65.20517/cdr.2021.55. Review.
Whitfield JR, Soucek L. The long journey to bring a Myc inhibitor to the clinic. J Cell Biol. 2021 Aug 2;220(8):e202103090. doi: 10.1083/jcb.202103090. Epub 2021 Jun 23.
Whitfield J, Soucek L. An “-omycs” Toolbox to Work with MYC. Methods Mol Biol. 2021;2318:1-11. doi: 10.1007/978-1-0716-1476-1_1.
Zacarías-Fluck MF, Jauset T, Martínez-Martín S, Kaur J, Casacuberta-Serra S, Massó-Vallés D, Serrano Del Pozo E, Martín-Fernández G, González-Larreategui Í, López-Estévez S, Brown-Swigart L, Beaulieu ME, Whitfield JR, Madan B, Virshup DM, Evan GI, Soucek L. The Wnt signaling receptor Fzd9 is essential for Myc-driven tumorigenesis in pancreatic islets. Life Sci Alliance. 2021 Mar 2;4(5):e201900490. doi: 10.26508/lsa.201900490. PMID: 33653688; PMCID: PMC8008953.
Pellanda P, Dalsass M, Filipuzzi M, Loffreda A, Verrecchia A, Castillo Cano V, Thabussot H, Doni M, Morelli MJ, Soucek L, Kress T, Mazza D, Mapelli M, Beaulieu ME, Amati B, Sabò A. Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription. EMBO J. 2021 May 17;40(10):e105464. doi: 10.15252/embj.2020105464. Epub 2021 Apr 1. PMID: 33792944; PMCID: PMC8126922.
Beaulieu ME, Castillo F, Soucek L. Structural and Biophysical Insights into the Function of the Intrinsically Disordered Myc Oncoprotein. Cells. 2020 Apr 22;9(4). pii: E1038. doi: 10.3390/cells9041038. Review.
Massó-Vallés D. and Soucek L. Blocking Myc to Treat Cancer: Reflecting on Two Decades of Omomyc. Cells. 2020, 9, 883; doi:10.3390/cells9040883. Review.
Daniel Massó-Vallés, Marie-Eve Beaulieu and Laura Soucek. “MYC, MYCL and MYCN as therapeutic targets in lung cancer”. Expert Opin Ther Targets. 2020 Jan 31. doi: 10.1080/14728222.2020.1723548. Review.
Nicole Sodir, Roderik Kortlever, Valentin Barthet, Tania Campos, Luca Pellegrinet, Steven Kupczak, Panayiotis Anastasiou, Lamorna Brown-Swigart, Laura Soucek, Mark Arends, Trevor Littlewood, and Gerard Evan. “Myc instructs and maintains pancreatic adenocarcinoma phenotype”. Cancer Discov. 2020 Jan 15. pii: CD-19-0435. doi: 10.1158/2159-8290.CD-19-0435. Article.
Rafael Ikemori, Marta Gabasa, Paula Duch, Miguel Vizoso, Paloma Bragado, Marselina Arshakyan, Iuliana-Cristiana Luis, Albert Marín, Sebastian Morán, Manuel Castro, Gemma Fuster, Sabrina Gea-Sorli, Toni Jauset, Laura Soucek, Luis Montuenga, Manel Esteller, Eduard Monsó, Víctor Ivo Peinado, Pere Gascón, Cristina Fillat, Frank Hilberg, Noemí Reguart, Jordi Alcaraz. “Epigenetic SMAD3 repression in tumor-associated fibroblasts impairs fibrosis and response to the antifibrotic drug nintedanib in lung squamous cell carcinoma”. Cancer Res. 2020 Jan 15;80(2):276-290. doi: 10.1158/0008-5472.CAN-19-0637. Article.
Mireia Pesarrodona, Toni Jauset, Zamira V. Díaz-Riascos, Alejandro Sánchez-Chardi, Marie-Eve Beaulieu, Joaquin Seras-Franzoso, Laura Sánchez-García, Ricardo Baltà-Foix, Sandra Mancilla, Yolanda Fernández, Ursula Rinas, Simó Schwartz Jr, Laura Soucek, Antonio Villaverde, Ibane Abasolo, and Esther Vázquez. “Targeting antitumoral proteins to breast cancer by local administration of functional inclusion bodies”. Advanced Sciences. Adv Sci (Weinh). 2019 Jul 24;6(18):1900849. doi: 10.1002/advs.201900849. A
Jonathan R. Whitfield and Laura Soucek. Editorial Overview: Peptides in Cancer. Current Opinion in Pharmacology. 2019 Jun 27. pii: S1471-4892(19)30045-1. Doi: 1016/j.coph.2019.06.001. Editorial.
Marie-Eve Beaulieu and Laura Soucek. Finding MYCure. Mol Cell Oncology. 2019. Doi: 1080/23723556.2019.1618178. Author’s View.
Ramón Y Cajal S, Sancho P, Soucek L, Peinado H, Abad M, Valiente M, Efeyan A, Pardo J, Quesada V, Jimeno J, Duque PM, Antón A, Varela I, Schuhmacher AJ. A spotlight on cancer researchers in Spain: new paradigms and disruptive ideas. Clin Transl Oncol. 2019 Aug 9. doi: 10.1007/s12094-019-02199-4.
Marie-Eve Beaulieu, Toni Jauset, Daniel Massó-Vallés, Sandra Martínez-Martín, Peter Rahl, Loïka Maltais, Mariano F. Zacarias-Fluck, Sílvia Casacuberta-Serra, Erika Serrano del Pozo, Christopher Fiore, Laia Foradada, Virginia Castillo Cano, Matthew Guenther, Eduardo Romero Sanz, Marta Oteo, Cynthia Tremblay, Génesis Martín, Danny Letourneau, Martin Montagne, Miguel Ángel Morcillo Alonso, Jonathan R. Whitfield, Pierre Lavigne and Laura Soucek. Intrinsic cell-penetrating activity propels Omomyc from proof of concept to viable anti-Myc therapy. Sci Trans Med. 2019 Mar 20;11(484). Doi: 10.1126/scitranslmed.aar5012. Article.
Irina Alimova, Angela Pierce, Etienne Danis, Andrew Donson, Diane K Birks, Andrea Griesinger, Nicholas K Foreman, Mariarita Santi, Laura Soucek, Sujatha Venkataraman & Rajeev Vibhakar. Inhibition of MYC attenuates tumor cell self-renewal and promotes senescence in SMARCB1 deficient Group 2 Atypical Teratoid Rhabdoid Tumors to suppress tumor growth in vivo. Int J Cancer. 2019 Apr 15;144(8):1983-1995. doi: 10.1002/ijc.31873. Article.
Sílvia Casacuberta-Serra and Laura Soucek. Myc and Ras, the Bonnie and Clyde of immune evasion. Translational Cancer Research. 2018 Feb ;7(Suppl 4):S457-S459. doi: 10.21037/tcr.2018.03.09.
Toni Jauset, Daniel Massó-Vallés, Sandra Martínez-Martín, Marie-Eve Beaulieu, Laia Foradada, Francesco Paolo Fiorentino, Jun Yokota, Bernard Haendler, Stephan Siegel, Jonathan R. Whitfield and Laura Soucek. BET inhibition is an effective approach against KRAS-driven PDAC and NSCLC. 2018 Apr 10;9(27):18734-18746. doi: 10.18632/oncotarget.24648. Article.
Chi Dang, E Premkumar Reddy, Kevan Shokat, and Laura Soucek. Drugging the ‘undruggable’ cancer targets. Nat Rev Cancer. 2017 Jun 23. doi: 10.1038/nrc.2017.36. Review.
Kim Pedersen, Faiz Bilal, Cristina Bernadó Morales, Maria Teresa Salcedo, Teresa Macarulla, Daniel Massó-Vallés, Vishnu Mohan, Ana Vivanco, Maria-Josep Carreras, Xavier Serres, Monder Abu-Suboh, Joaquim Balsells, Elena Allende, Irit Sagi, Laura Soucek, Josep Tabernero and Joaquín Arribas. Pancreatic cancer heterogeneity and response to Mek inhibition. 2017 Jun 5. doi: 10.1038/onc.2017.174. [Epub ahead of print]. Article.
Loïka Maltais, Martin Montagne, Mikaël Bédard, Cynthia Tremblay, Laura Soucek and Pierre Lavigne. Biophysical Characterization of the b-HLH-LZ of ΔMax, an Alternatively Spliced Isoform of Max Found in Tumor Cells: Towards the Validation of a Tumor Suppressor Role for the Max Homodimer. PLoS One. 2017 Mar 28; 12(3): e0174413. https://doi.org/10.1371/journal.pone.0174413. Article.
Jonathan R Whitfield, Marie-Eve Beaulieu, Laura Soucek. Strategies to inhibit Myc and their clinical applicability. Cell Dev. Biol., 23 February 2017 | https://doi.org/10.3389/fcell.2017.00010. Review.
Annette T. Byrne, Denis G. Alférez, Frederic Amant, Daniela Annibali, Joaquín Arribas, Andrew V. Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K. Chang, Robert B. Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S. Gail Eckhard, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G. Palmer, Daniel S. Peeper, Pier Giuseppe Pelicci, Alejandro Piris, Sergio Roman-Roman, Oscar M. Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti and Livio Trusolino. Interrogating open issues in cancer precision medicine using Patient-Derived Xenograft Models. Nat Rev Cancer. 2017 Jan 20. doi: 10.1038/nrc.2016.140. [Epub ahead of print]. Review.
E. Beaulieu, T. Jauset, D. Massó-Vallés, L. Soucek* and J.R. Whitfield. Mouse Models in Personalized Cancer Medicine. Chapter 6 of Cancer genetics and Genomics for Personalized Medicine. 2017. ISBN: 9789814669887. Book Chapter. *Corresponding author.
Soucek L, Torrens L, Pujades C and Claría J. Experimental Handbook of Translational Medicine. Medica UB. 2016. ISBN: 978-84-475-4030-3. Book chapter.
Daniel Massó-Vallés, Toni Jauset and Laura Soucek. Ibrutinib repurposing: from B cell malignancies to solid tumors. 2016 Jun 10;3(5-6):147-8.DOI: 10.18632/oncoscience.310. Review.
Francesco Paolo Fiorentino, Elvan Tokgün, Sònia Solé-Sánchez, Sabrina Giampaolo, Onur Tokgün, Toni Jauset, Takashi Kohno, Manuel Perucho, Laura Soucek, Jun Yokota. Growth Suppression by MYC Inhibition in Small Cell Lung Cancer Cells with TP53 and RB1 Inactivation. 2016 Apr 18. doi: 10.18632/oncotarget.8826. [Epub ahead of print] Article.
Cecconi F, Soucek L, Taub DD, Ziparo E. Live or Die: Choice Mechanisms in Stressed Cells. Mediators Inflamm. 2015; 2015:454863. Epub 2015 Oct 8. Editorial.
William H. Goodson III, Leroy Lowe, David O. Carpenter, Michael Gilbertson, Abdul Manaf Ali, Adela Lopez de Cerain Salsamendi, […], Laura Soucek, […], Zhiwei Hu. Assessing the Carcinogenic Potential of Low Dose Exposures to Chemical Mixtures in the Environment: The Challenge Ahead. 2015 Jun;36 Suppl 1:S254-96. doi: 10.1093/carcin/bgv039. Review.
Stephanie C. Casey, Monica Vaccari, Fahd Al-Mulla, Rabeah Al-Temaimi, Amedeo Amedei, Mary Helen Barcellos-Hoff, Dustin Brown, Marion Chapellier, […], Sandra Ryeom, Hosni K. Salem, Ivana Scovassi, Neetu Singh, Laura Soucek, Louis Vermeulen, Jonathan R. Whitfield, Jordan Woodrick, Annamaria Colacci, William H. Bisson, and Dean W. Felsher. Assessing the Carcinogenic Potential of Environmental Chemicals: The Tumor Microenvironment. 2015 Jun;36 Suppl 1:S160-83. doi: 10.1093/carcin/bgv035. Review.
Daniel Massó-Vallés, Toni Jauset, Erika Serrano, Nicole M. Sodir, Kim Pedersen, Nesrine I. Affara, Jonathan R. Whitfield, Marie-Eve Beaulieu, Gerard I. Evan, Laurence Elias, Joaquín Arribas and Laura Soucek. Ibrutinib exerts potent anti-fibrotic and anti-tumor activity in mouse transgenic and patient derived xenograft models of pancreatic adenocarcinoma. Cancer Res. 2015 Apr 15; 75(8): 1675-1681. Article.
Whitfield J, Littlewood T, Evan GI, Soucek L. The estrogen receptor fusion system in mouse models: a reversible switch. Cold Spring Harb Protoc. 2015 Mar 2;2015(3):pdb.top069815. doi: 10.1101/pdb.top069815. Book chapter.
Whitfield J, Littlewood T, Soucek L. Tamoxifen administration to mice. Cold Spring Harb Protoc. 2015 Mar 2;2015(3):pdb.prot077966. doi: 10.1101/pdb.prot077966. Book chapter.
Daniela Annibali, Jonathan R Whitfield, Emilia Favuzzi, Toni Jauset, Erika Serrano, Isabel Cuartas, Sara Redondo-Campos, Gerard Folch, Alba Gonzàlez-Juncà, Nicole M Sodir, Daniel Massó-Vallés, Marie-Eve Beaulieu, Lamorna B Swigart, Margaret M Mc Gee, Maria Patrizia Somma, Sergio Nasi, Joan Seoane, Gerard I Evan, and Laura Soucek. Myc Inhibition as a Therapeutic Strategy Against Glioma: a Role for Myc in Proficient Mitosis. Nat Communications. 2014 Aug 18;5:4632. doi: 10.1038/ncomms5632.
Book: “The Myc gene”, Methods and Protocols, Series: Methods in Molecular Biology, Vol. 1012. Soucek, Laura; Sodir, Nicole M. (Editors) 2013. A product of Humana Press.
Nicole M. Sodir and Laura Soucek. Chapter: The Myc world within reach. “Myc: Methods and Protocols” Book, Methods Mol Biol. 2013;1012:1-6. Book chapter.
Laura Soucek, Jonathan R. Whitfield, Nicole M. Sodir, Daniel Massó-Vallés, Erika Serrano, Anthony N. Karnezis, Lamorna Brown Swigart and Gerard I. Evan. Inhibition of Myc family proteins eradicates KRas-driven lung cancer in mice. Genes Dev. 2013 Mar 1;27(5):504-13. Article.
Whitfield J, Soucek L. Tumor microenvironment: becoming sick of Myc. Cell Mol Life Sci. 2012, 69(6), 931-934. Review.
Oscar M. Pello, Maria De Pizzol, Massimiliano Mirolo, Laura Soucek, Luca Zammataro, Angelo Amabile, Andrea Doni, Lamorna B. Swigart, Gerard I. Evan, Alberto Mantovani, Massimo Locati. c-Myc controls alternative activation of human macrophages and tumor-associated macrophage biology. 2012, 119(2), 411-421. Article.
Laura Soucek, Joseph J Buggy, Roderik Kortlever, Shanthi Adimoolam, Lamorna Brown Swigart and Gerard Evan. Modeling mast cell inhibition by PCI-32765 as potential therapy for insulinoma. 2011; 13(11):1093–100. Article.
Mauro Savino, Daniela Annibali, Nicoletta Carucci, Laura Soucek, Gerard Evan, Sergio Nasi. The Action Mechanism of the Myc Inhibitor Termed Omomyc May Give Clues on How to Target Myc for Cancer Therapy. PLoS One. 2011;6(7):e22284. Epub 2011 Jul 21. Article.
Nicole M Sodir, Lamorna Brown Swigart, Anthony N Karnezis, Douglas Hanahan, Gerard Evan and Laura Soucek. Endogenous Myc maintains the tumor microenvironment. Genes Dev. 2011 May 1;25(9):907-16. Epub 2011 Apr 8.
Fukazawa T, Maeda Y, Matsuoka J, Yamatsuji T, Shigemitsu K, Morita I, Faiola F, Durbin ML, Soucek L, Naomoto Y. Inhibition of Myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc. Anticancer Res. 2010 Oct;30(10):4193-200.
Soucek L, Evan GI. The ups and downs of Myc biology. Curr Opin Genet Dev. 2010 Feb;20(1):91-95. Epub 2009 Dec 3. Review.
Andrew Finch*, Laura Soucek*, Melissa Junttila, Lamorna Brown Swigart and Gerard I. Evan. Acute over-expression of Myc in intestinal epithelium recapitulates some but not all the changes elicited by Wnt/β-catenin pathway activation. Mol Cell Biol. 2009 Oct;29(19):5306-15. Epub 2009 Jul 27. Article. *Joint first authors
Laura Soucek, Jonathan Whitfield, Carla P. Martins, Andrew J. Finch, Nicole M. Sodir, Lamorna Brown Swigart, Sergio Nasi and Gerard I. Evan. Modelling Myc inhibition as a cancer therapy. Nature. 2008 Oct 2;455(7213):679-83. Epub 2008 Aug 17. Article.
Soucek L, Lawlor ER, Soto D, Shchors K, Swigart LB, Evan GI. Mast cells are required for angiogenesis and macroscopic expansion of Myc-induced pancreatic islet tumors.
Nat Med. 2007 Oct;13(10):1211-8. Epub 2007 Sep 30. Article.
Finch A, Prescott J, Shchors K, Hunt A, Soucek L, Dansen TB, Swigart LB, Evan GI. Bcl-x(L) gain of function and p19(ARF) loss of function cooperate oncogenically with Myc in vivo by distinct mechanisms. Cancer Cell. 2006 Aug;10(2):113-120. Article.
Elizabeth R. Lawlor, Laura Soucek, Lamorna Brown-Swigart, Ksenya Shchors, Uli Bialucha, Gerard I. Evan. Reversible Kinetic Analysis of Myc Targets In vivo Provides Novel Insights into Myc-Mediated Tumorigenesis. Cancer Res. 2006 May 1;66(9):4591-601. Article.
Maria A. Christophorou, Dionisio Martin-Zanca, Laura Soucek, Elizabeth Lawlor, Emmy Verschuren, Lamorna Brown-Swigart and Gerard I. Evan. Temporal dissection of p53 function in vitro and in vivo. Nature Genetics. 2005 Jul;37(7):718-26. Article.
Laura Soucek, Sergio Nasi, and Gerard Evan. Omomyc expression in skin prevents Myc-induced papillomatosis. Cell Death Differ. 2004 Sep;11(9):1038-45. Article.
Satoshi Kanasawa, Laura Soucek, Gerard Evan, Takashi Okamoto, and B. Matija Peterlin. c-Myc recruits P-TEFb for transcription, cellular proliferation and apoptosis. Oncogene. 2003 Aug 28;22(36):5707-11. Article.
Laura Soucek and Gerard Evan. Myc – is this the oncogene from Hell?. Cancer Cell. 2002 June; 1(5): 406-408. Review.
Laura Soucek, Richard Jucker, Laura Panacchia, Ruggero Ricordy, Franco Tatò, and Sergio Nasi. Omomyc, a Potential Myc Dominant Negative, Enhances Myc-induced Apoptosis . Cancer Res. 2002; 62: 3507-3510. Article.
Mandolesi G, Gargano S, Pennuto M, Illi B, Molfetta R, Soucek L, Mosca L, Levi A, Jucker R, Nasi S. NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction. FEBS Lett. 2002. ¡ 510(1-2):50-6. Article.
Sergio Nasi, Roberta Ciarapica, Richard Jucker, Jessica Rosati and Laura Soucek. Making decisions through Myc. FEBS. 2001. 490(3): 153-162. Review.
Sergio Nasi and Laura Soucek. p53 Gene e Proteina, Enciclopedia Medica Italiana, Tomo III, 2000, 4313-4323. Book chapter.
Soucek L., Citterich M.H., Sacco A., Jucker R., Cesareni G. and Nasi S. Design and properties of a Myc derivative that efficiently homodimerizes. Oncogene. 1998, 17(19): 2463-2472. Article.

Projects

Project Title: Identification of clinical biormakers of response to MYC inhibition in cancer treatment.
Principal Investigators: Laura Soucek
Funding Agency: Spanish Ministry of Economy, Industry and Competitiveness “Retos de Colaboración” Grant.
Duration: 2020-2023

Proyectos I+D+i en «líneas estratégicas» 2021

Title: Uso de la inhibición de MYC para superar la resistencia a la inmunoterapia en NSCLC impulsado por KRAS con diversos perfiles mutacionales (MYCOMBIO)

Project PLEC2021-007959, funded by MCIN/AEI/10.13039/501100011033 and UE NextGenerationEU/PRTR”, for which aid has been granted in the form of a subsidy for a total amount of €399,771.00.

IP: Laura Soucek

Instituto de Salud Carlos III: Proyectos FIS de Investigación en Salud.
Title: Validation of new anti-Myc therapy in Melanoma. 2020-2023.
PI: Laura Soucek
Awarded in 2019.

Fundació La Marató de TV3
Title: Overcoming immunotherapeutic resistance through Myc inhibition in KRas-driven NSCLC with diverse mutational landscape.
2020-2022.
Project Director: Laura Soucek. Co-participant: Silvestre Vicent Cambra.

Canadian Institutes of Health Research Grant
Title: Development of cancer therapies targeting Myc with cell penetrating b-HLH-LZ domains.
2018-2023.
Role: Co-applicant.

Title: Estrategias para incrementar el potencial clínico de inhibidores de MYC: identificación de biomarcadores, sinergias y nuevas indicaciones

Role: Co-applicant como entidad OPI. I+D+I en el proyecto de la convocatoria 2019 RETOS-COLABORACIÓN, bajo la referencia externa de proyecto: RTC2019-007067-1, para el cual se ha otorgado una ayuda en forma de subvención por un importe total de 668.225,48€
2020-2023.
PI: Laura Soucek

Proyecto financiado por el Ministerio de Ciencia e Innovación

El presente proyecto está cofinanciado por el Fondo Europeo de Desarrollo Regional. Objetivo Temático: Promover el desarrollo tecnológico, la innovación y una investigación de calidad.

H2020 INFRAIA 2017
Title: EDIReX: EurOPDX Distributed Infrastructure for Research on patient-derived cancer Xenografts.
2017-2021.
Role: Co-applicant5. I+D+I en Líneas Estratégicas en colaboración público-privada, Spanish Ministry of Economy, Industry and Competitiveness. Title: Using MYC inhibition to overcome immunotherapy resistance in KRAS-driven NSCLC with diverse mutational profiles (MYCOMBIO).
2021-2024.
PI: Laura Soucek

Proyecto financiado por el Ministerio de Economía y Competitividad

El presente proyecto está cofinanciado por el Fondo Europeo de Desarrollo Regional. Objetivo Temático: Promover el desarrollo tecnológico, la innovación y una investigación de calidad.

Ph.D. Fellowships from FIS– Fondo de Investigación en Salud (Health Research Fund) and Ministerio de Educación y Formación Profesional (Spanish Ministry of Education and Professional Training) University Professorship Training (FPU), awarded to Fabio Giuntini and Íñigo Larreategui, respectively.

Chiara Giorgetti Award from the Spanish Association of Metastatic Breast Cancer. Title: “Combining MYC and PARP inhibitors as a novel therapeutic strategy against triple-negative breast cancer”. 2022-2024. PI: Laura Soucek.

2nd BBVA Foundation Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI II), VHIO-FBBVA Collaboration. Title: “Understanding the tumor microenvironment to identify therapeutic targets and improve the response to immune checkpoint inhibitors” and “Understanding the mechanisms of resistance to IT and immune evasion to targeted therapies and designing new rational combinatory treatments”. 2022-2025. PI: Laura Soucek.

SME Instrument Phase II to Peptomyc from the European Commission. “Innovative cancer therapy through Myc inhibition: taking OMO-103 to market”. 2019-2023. Main contact: Laura Soucek

Project Title: CLINICAL PROOF-OF-CONCEPT OF A FIRST-IN-CLASS MYC INHIBITOR IN COMBINATION THERAPY AND EXPANSION OF ITS DEVELOPMENT PLAN (CLINIMYC). FUnding entity: Agencia Estatal de Investigación – Ministerio de Ciencia e Innovación. Ref: CPP2022-009808. Duration: 10/03/2023 – 09/03/2026. Coordinator: Peptomyc, SL. PI VHIO: Laura Soucek

Project Title: Maximizing the use of a first clinically viable MYC inhibitor – MYCiMAX. Reference Number: 101142260. Fund Entity: European Research Council (ERC). European Commission. Duration: 01/05/2024-30/04/2029. PI: Laura Soucek

Models of Cancer Therapies Group

Laura Soucek

Group Leader

Biosketch

Jonathan R. Whitfield

Senior Researcher

Biosketch

Research Lines

Team

Group Leader

Laura Soucek

Senior Researcher

Jonathan R. Whitfield

Research Associate

Mariano F. Zacarías-Fluck

Post-Doctoral Fellows

Ana Lopez Garza

Technicians

Judit Grueso

Erika Serrano del Pozo

Romina Mariel Rodriguez

Manrique Jose Valdez-Bango

PhD Students

Daniel Capitán Leo

Fabio Giuntini

Íñigo González-Larreategui

Publications

Projects

Project Funding

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