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Sarcoma Translational Research Group

Portfolio Item Sarcoma Translational Research Group
BIOMEDICAL RESEARCH

Sarcoma encompasses >70 entities of mesenchymal origin, constituting 1-2% of all cancers. From a biological perspective sarcomas can be classified into two broad categories: genomically simple sarcomas driven by simple genetic alterations, such as translocations or specific activating mutations; and tumors with complex and unbalanced genomic aberrations. Each of these categories include diverse sarcomas subtypes often with profound differences in their molecular makeup, course of disease and therapeutic approach.

Our group focus on the study of sarcomas with oncogenic dependency on specific drivers of disease. Among these, gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal neoplasm and constitutes a paradigmatic model for studying oncogene addiction and identifying structural and functional mechanisms for drug response and resistance.

Ongoing efforts aim at achieving a deeper biological understanding of GIST and other sarcomas to advance drug development. The heterogeneity of mechanisms of resistance represents one of the major challenges in improving outcomes for these patients. We therefore seek to identify crucial molecules and signaling mechanisms in GIST biology that can serve as therapeutic vulnerabilities. The involvement of the ubiquitin pathway and by-pass signaling mechanisms have become a major focus over recent years.

We also perform high-throughput genomic and transcriptomic studies to decipher the evolving patterns of resistance in GIST throughout the course of disease, as well as investigate liquid biopsy in sarcoma to provide robust evidence that will help to more precisely guide treatment decisions by plasma sequencing. In addition, the GISTomics project, a European initiative driven by our group, aims to advance insights into the landscape of GIST evolution. In the same direction, our group is leading international initiatives to investigate the role of circulating tumor DNA (ctDNA) in GISTs and other sarcomas with the double aim of obtaining insights into the biological features of these tumors in heavily pretreated patients, and determine the main avenues for its clinical implementation.

Beyond GIST, our group has initiated new lines of research focused on other sarcoma subtypes, including muscle-derived sarcomas (leiomyosarcoma and rhabdomyosarcoma), angiosarcoma, and liposarcoma. Functional precision medicine is a major focus of research in these neoplasms.

Our aim is to have a true clinical impact by improving the daily treatment and care of our patients. We are proud to report that our Sarcoma Multidisciplinary Unit has been designated as an Expert Sarcoma Center of the European Reference Network ERN-EURACAN, and thus constitutes an optimal setting for translating cancer discovery into clinical benefits.

César Serrano
Group Leader
Biosketch

Research Lines

  • Identification of critical molecular mediators of oncogenic signaling in sarcomas.
  • Characterization of response and resistance mechanisms to targeted therapies in sarcomas.
  • Preclinical modelling and validation of therapeutic strategies to translate at the clinical level.
  • Clinical drug development in sarcomas across phase I to phase III clinical trials.

Figure: Gastrointestinal stromal tumor (GIST) is the most common malignant mesenchymal tumor and a successful and paradigmatic model to dissect mechanisms of response and resistance to molecularly targeted agents. Ongoing research from our group is advancing this knowledge in two directions: first, we are interrogating mutation-based mechanisms affecting the sensitivity to approved KIT inhibitors.

Second, we are investigating the cytogenetic progression that fuels GIST growth. These findings have a direct impact on the future of drug development in GIST and other diseases (Figure from Serrano & George, Clin Cancer Res 2020; 26: 923-934.).

Team

Group Leader
César Serrano
Oncologist
Carlo M. Cicala
Post-Doctoral Fellow
Alfonso García Valverde
Pre-Doctoral Fellows
Daniel Pilco Janeta
David Gómez Peregrina
Iván Olivares Rivas
Gemma Mur Bonet
Jon Ander Aguirre Carrillo
Júlia Caparrós Mateos
Senior Technician
Jordi Rosell Aluja
Graduate Student
Mar Peláez Parra

Publications

Most Relevant Scientific Publications

  • Serrano C, Rothschild S, Villacampa G, Heinrich MC, George S, Blay JY, Sicklick JK, Schwartz GK, Rastogi S, Jones RL, Rutkowski P, Somaiah N, Navarro V, Evans D, Trent JC. Rethinking placebos: embracing synthetic control arms in clinical trials for rare tumors. Nat Med. 2023 Nov;29(11):2689-2692.
  • Serrano C, Martín-Broto J, Asencio-Pascual JM, López-Guerrero JA, Rubió-Casadevall J, Bagué S, García-Del-Muro X, Fernández-Hernández JÁ, Herrero L, López-Pousa A, Poveda A, Martínez-Marín V. 2023 GEIS Guidelines for gastrointestinal stromal tumors. Ther Adv Med Oncol. 2023 Aug 24;15:17588359231192388.
  • Serrano C, Bauer S, Gómez-Peregrina D, Kang YK, Jones RL, Rutkowski P, Mir O, Heinrich MC, Tap WD, Newberry K, Grassian A, Shi H, Bialick S, Schöffski P, Pantaleo MA, von Mehren M, Trent JC, George S. Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib. Ann Oncol. 2023 Jul;34(7):615-625.
  • Pestana RC, Serrano C. Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database. Front Oncol. 2023 Jan 18;12:1079909.
  • Schaefer IM, DeMatteo RP, Serrano C. The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor. Am Soc Clin Oncol Educ Book. 2022 Apr;42:1-15.
  • Ravegnini G, Fosso B, Ricci R, Gorini F, Turroni S, Serrano C, Pilco-Janeta DF, Zhang Q, Zanotti F, De Robertis M, Nannini M, Pantaleo MA, Hrelia P, Angelini S. Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options. Cancer Sci. 2022 Aug;113(8):2590-2599.
  • 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.
  • García-Valverde A, Rosell J, Sayols S, Gómez-Peregrina D, Pilco-Janeta DF, Olivares-Rivas I, de Álava E, Maurel J, Rubió-Casadevall J, Esteve A, Gut M, Valverde C, Barretina J, Carles J, Demetri GD, Fletcher JA, Arribas J, Serrano C. E3 ubiquitin ligase Atrogin-1 mediates adaptive resistance to KIT-targeted inhibition in gastrointestinal stromal tumor. Oncogene. 2021 Dec;40(48):6614-6626.
  • Bauer S, Heinrich MC, George S, Zalcberg JR, Serrano C, Gelderblom H, Jones RL, Attia S, D’Amato G, Chi P, Reichardt P, Meade J, Su Y, Ruiz-Soto R, Blay JY, von Mehren M, Schöffski P. Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous KIT/PDGFRA Mutations in the Phase III INVICTUS Study. Clin Cancer Res. 2021 Dec 1;27(23):6333-6342.
  • Lostes-Bardaji MJ, García-Illescas D, Valverde C, Serrano C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol. 2021 Jan 7;13:1758835920986498.
  • Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142.
  • Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D’Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a doubleblind, randomised, placebocontrolled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934.
  • Serrano C, George S. Gastrointestinal Stromal Tumor: Challenges and Opportunities for a New Decade. Clin Cancer Res. 2020 Oct 1;26(19):5078-5085.
    Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946.
  • Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer. 2019 Mar;120(6):612-620.
  • Serrano C, García-Del-Muro X, Valverde C, Sebio A, Durán J, Manzano A, Pajares I, Hindi N, Landolfi S, Jiménez L, Rubió-Casadevall J, Estival A, Lavernia J, Safont MJ, Pericay C, Díaz-Beveridge R, Martínez-Marín V, Vicente-Baz D, Vivancos A, Hernández-Losa J, Arribas J, Carles J. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib. Oncologist. 2019 May;24(5):680-687.
    George S, Serrano C, Hensley ML, Ray-Coquard I. Soft Tissue and Uterine Leiomyosarcoma. J Clin Oncol. 2018 Jan 10;36(2):144-150.
  • Garner AP, Gozgit JM, Anjum R, Vodala S, Schrock A, Zhou T, Serrano C, Eilers G, Zhu M, Ketzer J, Wardwell S, Ning Y, Song Y, Kohlmann A, Wang F, Clackson T, Heinrich MC, Fletcher JA, Bauer S, Rivera VM. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014 Nov 15;20(22):5745-5755.
  • George S, Barysauskas C, Serrano C, Oduyebo T, Rauh-Hain JA, Del Carmen MG, Demetri GD, Muto MG. Retrospective cohort study evaluating the impact of intraperitoneal morcellation on outcomes of localized uterine leiomyosarcoma. Cancer. 2014 Oct 15;120(20):3154-8.
  • Serrano C, Wang Y, Mariño-Enríquez A, Lee JC, Ravegnini G, Morgan JA, Bertagnolli MM, Beadling C, Demetri GD, Corless CL, Heinrich MC, Fletcher JA. KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation. J Clin Oncol. 2015 Aug 1;33(22):e93-6.

All Publications

  • Martin-Broto J, Valverde C, Hindi N, Vincenzi B, Martinez-Trufero J, Grignani G, Italiano A, Lavernia J, Vallejo A, Tos PD, Le Loarer F, Gonzalez-Campora R, Ramos R, Hernández-Jover D, Gutierrez A, Serrano C, Monteagudo M, Letón R, Robledo M, Moura DS, Martin-Ruiz M, López-Guerrero JA, Cruz J, Fernandez-Serra A, Blay JY, Fumagalli E, Martinez-Marin V. REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial. Mol Cancer. 2023 Aug 9;22(1):127. doi: 10.1186/s12943-023-01832-9. PMID: 37559050; PMCID: PMC10413507.
  • Pestana RC, Serrano C. Analysis of histology-agnostic targets among soft tissue and bone sarcomas in the AACR GENIE database. Front Oncol. 2023 Jan 18;12:1079909. doi: 10.3389/fonc.2022.1079909. PMID: 36741731; PMCID: PMC9890057.
  • Di Vito A, Ravegnini G, Gorini F, Aasen T, Serrano C, Benuzzi E, Coschina E, Monesmith S, Morroni F, Angelini S, Hrelia P. The multifaceted landscape behind imatinib resistance in gastrointestinal stromal tumors (GISTs): A lesson from ripretinib. Pharmacol Ther. 2023 Aug;248:108475. doi: 10.1016/j.pharmthera.2023.108475. Epub 2023 Jun 10. PMID: 37302758.
  • Martin-Broto J, Valverde C, Hindi N, Vincenzi B, Martinez-Trufero J, Grignani G, Italiano A, Lavernia J, Vallejo A, Tos PD, Le Loarer F, Gonzalez-Campora R, Ramos R, Hernández-Jover D, Gutierrez A, Serrano C, Monteagudo M, Letón R, Robledo M, Moura DS, Martin-Ruiz M, López-Guerrero JA, Cruz J, Fernandez-Serra A, Blay JY, Fumagalli E, Martinez-Marin V. REGISTRI: Regorafenib in first-line of KIT/PDGFRA wild type metastatic GIST: a collaborative Spanish (GEIS), Italian (ISG) and French Sarcoma Group (FSG) phase II trial. Mol Cancer. 2023 Aug 9;22(1):127. doi: 10.1186/s12943-023-01832-9. PMID: 37559050; PMCID: PMC10413507.
  • Ruiz-Demoulin S, Trenquier E, Dekkar S, Deshayes S, Boisguérin P, Serrano C, de Santa Barbara P, Faure S. LIX1 Controls MAPK Signaling Reactivation and Contributes to GIST-T1 Cell Resistance to Imatinib. Int J Mol Sci. 2023 Apr 12;24(8):7138. doi: 10.3390/ijms24087138. PMID: 37108337; PMCID: PMC10138740.
  • Serrano C, Rothschild S, Villacampa G, Heinrich MC, George S, Blay JY, Sicklick JK, Schwartz GK, Rastogi S, Jones RL, Rutkowski P, Somaiah N, Navarro V, Evans D, Trent JC. Rethinking placebos: embracing synthetic control arms in clinical trials for rare tumors. Nat Med. 2023 Nov;29(11):2689-2692. doi: 10.1038/s41591-023-02578-z. PMID: 37828359.
  • He W, Xu L, Ding J, Song L, Yang W, Klooster I, Pilco-Janeta DF, Serrano C, Fang H, Jiang G, Wang X, Yu J, Ou WB. Co-targeting of ACK1 and KIT triggers additive anti-proliferative and -migration effects in imatinib-resistant gastrointestinal stromal tumors. Biochim Biophys Acta Mol Basis Dis. 2023 Jun;1869(5):166690. doi: 10.1016/j.bbadis.2023.166690. Epub 2023 Mar 13. PMID: 36921738.
  • Proaño-Pérez E, Serrano-Candelas E, García-Valverde A, Rosell J, Gómez-Peregrina D, Navinés-Ferrer A, Guerrero M, Serrano C, Martín M. The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth. Cancer Gene Ther. 2023 Feb;30(2):245-255. doi: 10.1038/s41417-022-00539-1. Epub 2022 Oct 14. Erratum in: Cancer Gene Ther. 2022 Nov 18;: PMID: 36241703.
  • Serrano C, Bauer S. New Tyrosine Kinase Inhibitors for the Treatment of Gastrointestinal Stromal Tumors. Curr Oncol Rep . 2022 Feb;24(2):151-159.
  • Schaefer IM, DeMatteo RP, Serrano C. The GIST of Advances in Treatment of Advanced Gastrointestinal Stromal Tumor. Am Soc Clin Oncol Educ Book . 2022 Apr;42:1-15.
  • Ravegnini G, Fosso B, Ricci R, Gorini F, Turroni S, Serrano C, Pilco-Janeta DF, Zhang Q, Zanotti F, De Robertis M, Nannini M, Pantaleo MA, Hrelia P, Angelini S. Analysis of microbiome in gastrointestinal stromal tumors: Looking for different players in tumorigenesis and novel therapeutic options. Cancer Sci . 2022 Aug;113(8):2590-2599.
  • Fernández-Hernández JA, Cantín-Blázquez S, García-Somacarrera E, Varo-Pérez E, González-López JA, Asencio-Pascual JM, Mendiola M, Serrano C, García-Granero E, Artigas-Raventós V. Avances en tumores del estroma gastrointestinal: ¿hacia dónde vamos? Cir Cir . 2022;90(2):267-277. English.
  • Proaño-Pérez E, Serrano-Candelas E, García-Valverde A, Rosell J, Gómez-Peregrina D, Navinés-Ferrer A, Guerrero M, Serrano C, Martín M. The microphthalmia-associated transcription factor is involved in gastrointestinal stromal tumor growth. Cancer Gene Ther . 2022 Oct 14.
  • Ravegnini G, Nannini M, Indio V, Serrano C, Gorini F, Astolfi A, Di Vito A, Morroni F, Pantaleo MA, Hrelia P, Angelini S. miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs. Int J Mol Sci . 2022 Oct 14;23(20):12248.
  • 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.
  • Bauer S, Heinrich MC, George S, Zalcberg JR, Serrano C, Gelderblom H, Jones RL, Attia S, D’Amato G, Chi P, Reichardt P, Meade J, Su Y, Ruiz-Soto R, Blay JY, von Mehren M, Schöffski P. Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous KIT/PDGFRA Mutations in the Phase III INVICTUS Study. Clin Cancer Res. 2021 Dec 1;27(23):6333-6342.
  • García-Valverde A, Rosell J, Sayols S, Gómez-Peregrina D, Pilco-Janeta DF, Olivares-Rivas I, de Álava E, Maurel J, Rubió-Casadevall J, Esteve A, Gut M, Valverde C, Barretina J, Carles J, Demetri GD, Fletcher JA, Arribas J, Serrano C. E3 ubiquitin ligase Atrogin-1 mediates adaptive resistance to KIT-targeted inhibition in gastrointestinal stromal tumor. Oncogene. 2021 Dec;40(48):6614-6626.
  • Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142.
  • Lostes-Bardaji MJ, García-Illescas D, Valverde C, Serrano C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol. 2021 Jan 7;13:1758835920986498.
  • Gómez-Peregrina D, García-Valverde A, Pilco-Janeta D, Serrano C. Liquid Biopsy in Gastrointestinal Stromal Tumors: Ready for Prime Time? Curr Treat Options Oncol. 2021 Feb 27;22(4):32.
  • George S, Jones RL, Bauer S, Kang YK, Schöffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent J, Rutkowski P, Patel S, Chawla SP, Meiri E, Gordon M, Zhou T, Roche M, Heinrich MC, von Mehren M. Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy. Oncologist. 2021 Apr;26(4):e639-e649.
  • Zalcberg JR, Heinrich MC, George S, Bauer S, Schöffski P, Serrano C, Gelderblom H, Jones RL, Attia S, D’Amato G, Chi P, Reichardt P, Somaiah N, Meade J, Reichert V, Shi K, Sherman ML, Ruiz-Soto R, von Mehren M, Blay JY. Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study. Oncologist. 2021 Nov;26(11):e2053-e2060.
  • Joseph CP, Abaricia SN, Angelis MA, Polson K, Jones RL, Kang YK, Riedel RF, Schöffski P, Serrano C, Trent J, Tetzlaff ED, Si TD, Zhou T, Doyle A, Bauer S, Roche M, Havnaer T. Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors. Oncologist. 2021 Apr;26(4):e622-e631.
  • Ravegnini G, Serrano C, Ricci R, Zhang Q, Terrenato I, Graziosi A, Valori G, Landolfi S, Hrelia P, Angelini S. miRNA landscape in primary tumors and matched metastases in gastrointestinal stromal tumors. Epigenomics. 2021 Mar;13(5):369-377.
  • Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142.
  • Pilco-Janeta DF, García-Valverde A, Gomez-Peregrina D, Serrano C. Emerging drugs for the treatment of gastrointestinal stromal tumors. Expert Opin Emerg Drugs. 2021 Mar;26(1):53-62.
  • Serrano C. New treatments in advanced gastrointestinal stromal tumor. Curr Opin Oncol. 2021 Jul 1;33(4):323-328.
  • Gupta A, Singh J, García-Valverde A, Serrano C, Flynn DL, Smith BD. Ripretinib and MEK inhibitors synergize to induce apoptosis in preclinical models of GIST and Systemic Mastocytosis. Mol Cancer Ther. 2021 May 4.
  • Serrano C. New treatments in advanced gastrointestinal stromal tumor. Curr Opin Oncol. 2021 Apr 16.
    Pilco-Janeta DF, García-Valverde A, Gomez-Peregrina D, Serrano C. Emerging drugs for the treatment of gastrointestinal stromal tumors. Expert Opin Emerg Drugs. 2021 Mar;26(1):53-62.
  • Gómez-Peregrina D, García-Valverde A, Pilco-Janeta D, Serrano C. Liquid Biopsy in Gastrointestinal Stromal Tumors: Ready for Prime Time? Curr Treat Options Oncol. 2021 Feb 27;22(4):32.
  • George S, Jones RL, Bauer S, Kang YK, Schöffski P, Eskens F, Mir O, Cassier PA, Serrano C, Tap WD, Trent J, Rutkowski P, Patel S, Chawla SP, Meiri E, Gordon M, Zhou T, Roche M, Heinrich MC, von Mehren M. Avapritinib in Patients With Advanced Gastrointestinal Stromal Tumors Following at Least Three Prior Lines of Therapy. Oncologist. 2021 Apr;26(4):e639-e649.
  • Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, Schöffski P, Cassier PA, Mir O, Chawla SP, Eskens FALM, Rutkowski P, Tap WD, Zhou T, Roche M, Bauer S. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142.
  • Ravegnini G, Serrano C, Ricci R, Zhang Q, Terrenato I, Graziosi A, Valori G, Landolfi S, Hrelia P, Angelini S. miRNA landscape in primary tumors and matched metastases in gastrointestinal stromal tumors. Epigenomics. 2021 Mar;13(5):369-377.
  • Lostes-Bardaji MJ, García-Illescas D, Valverde C, Serrano C. Ripretinib in gastrointestinal stromal tumor: the long-awaited step forward. Ther Adv Med Oncol. 2021 Jan 7;13.
  • Joseph CP, Abaricia SN, Angelis MA, Polson K, Jones RL, Kang YK, Riedel RF, Schöffski P, Serrano C, Trent J, Tetzlaff ED, Si TD, Zhou T, Doyle A, Bauer S, Roche M, Havnaer T. Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors. Oncologist. 2021 Apr;26(4):e622-e631.
  • Serrano C, George S. Gastrointestinal Stromal Tumor: Challenges and Opportunities for a New Decade. Clin Cancer Res. 2020 Oct 1;26(19):5078-5085.
    Demetri GD, Antonescu CR, Bjerkehagen B, Bovée JVMG, Boye K, Chacón M, Dei Tos AP, Desai J, Fletcher JA, Gelderblom H, George S, Gronchi A, Haas RL, Hindi N, Hohenberger P, Joensuu H, Jones RL, Judson I, Kang YK, Kawai A, Lazar AJ, Le Cesne A, Maestro R, Maki RG, Martín J, Patel S, Penault-Llorca F, Premanand Raut C, Rutkowski P, Safwat A, Sbaraglia M, Schaefer IM, Shen L, Serrano C, Schöffski P, Stacchiotti S, Sundby Hall K, Tap WD, Thomas DM, Trent J, Valverde C, van der Graaf WTA, von Mehren M, Wagner A, Wardelmann E, Naito Y, Zalcberg J, Blay JY. Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas: expert recommendations from the World Sarcoma Network. Ann Oncol. 2020 Nov;31(11):1506-1517.
  • Heinrich MC, Jones RL, von Mehren M, Schöffski P, Serrano C, Kang YK, Cassier PA, Mir O, Eskens F, Tap WD, Rutkowski P, Chawla SP, Trent J, Tugnait M, Evans EK, Lauz T, Zhou T, Roche M, Wolf BB, Bauer S, George S. Avapritinib in advanced PDGFRA D842V-mutant gastrointestinal stromal tumour (NAVIGATOR): a multicentre, open-label, phase 1 trial. Lancet Oncol. 2020 Jul;21(7):935-946.
  • Blay JY, Serrano C, Heinrich MC, Zalcberg J, Bauer S, Gelderblom H, Schöffski P, Jones RL, Attia S, D’Amato G, Chi P, Reichardt P, Meade J, Shi K, Ruiz-Soto R, George S, von Mehren M. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 Jul;21(7):923-934.
  • García-Valverde A, Rosell J, Serna G, Valverde C, Carles J, Nuciforo P, Fletcher JA, Arribas J, Politz O, Serrano C. Preclinical Activity of PI3K Inhibitor Copanlisib in Gastrointestinal Stromal Tumor. Mol Cancer Ther. 2020 Jun;19(6):1289-1297.
  • Serrano C, Vivancos A, López-Pousa A, Matito J, Mancuso FM, Valverde C, Quiroga S, Landolfi S, Castro S, Dopazo C, Sebio A, Virgili AC, Menso MM, Martín-Broto J, Sansó M, García-Valverde A, Rosell J, Fletcher JA, George S, Carles J, Arribas J. Clinical value of next generation sequencing of plasma cell-free DNA in gastrointestinal stromal tumors. BMC Cancer. 2020 Feb 5;20(1):99.
  • Serrano C, Leal A, Kuang Y, Morgan JA, Barysauskas CM, Phallen J, Triplett O, Mariño-Enríquez A, Wagner AJ, Demetri GD, Velculescu VE, Paweletz CP, Fletcher JA, George S. Phase I Study of Rapid Alternation of Sunitinib and Regorafenib for the Treatment of Tyrosine Kinase Inhibitor Refractory Gastrointestinal Stromal Tumors. Clin Cancer Res. 2019 Dec 15;25(24):7287-7293.
  • Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu MJ, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Complementary activity of tyrosine kinase inhibitors against secondary KIT mutations in imatinib-resistant gastrointestinal stromal tumors. Br J Cancer. 2019 Mar;120(6):612-620.
  • Serrano C, García-Del-Muro X, Valverde C, Sebio A, Durán J, Manzano A, Pajares I, Hindi N, Landolfi S, Jiménez L, Rubió-Casadevall J, Estival A, Lavernia J, Safont MJ, Pericay C, Díaz-Beveridge R, Martínez-Marín V, Vicente-Baz D, Vivancos A, Hernández-Losa J, Arribas J, Carles J. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib. Oncologist. 2019 May;24(5):680-687.
  • Serrano C, García-Del-Muro X, Valverde C, Sebio A, Durán J, Manzano A, Pajares I, Hindi N, Landolfi S, Jiménez L, Rubió-Casadevall J, Estival A, Lavernia J, Safont MJ, Pericay C, Díaz-Beveridge R, Martínez-Marín V, Vicente-Baz D, Vivancos A, Hernández-Losa J, Arribas J, Carles J. Clinicopathological and Molecular Characterization of Metastatic Gastrointestinal Stromal Tumors with Prolonged Benefit to Frontline Imatinib. Oncologist. 2019 May;24(5):680-687.
  • Ravegnini G, Serrano C, Simeon V, Sammarini G, Nannini M, Roversi E, Urbini M, Ferrè F, Ricci R, Tarantino G, Pantaleo MA, Hrelia P, Angelini S. The rs17084733 variant in the KIT 3′ UTR disrupts a miR-221/222 binding site in gastrointestinal stromal tumour: a sponge-like mechanism conferring disease susceptibility. Epigenetics. 2019 Apr 13:1-13.
  • Serrano C, Mariño-Enríquez A, Tao DL, Ketzer J, Eilers G, Zhu M, Yu C, Mannan AM, Rubin BP, Demetri GD, Raut CP, Presnell A, McKinley A, Heinrich MC, Czaplinski JT, Sicinska E, Bauer S, George S, Fletcher JA. Complementary activity of tyrosine kinase inhibitors against secondary kit mutations in imatinib-resistant gastrointestinal stromal tumours. Br J Cancer. 2019 Mar;120(6):612-620.
  • Ravegnini G, Sammarini G, Serrano C, Nannini M, Pantaleo MA, Hrelia P, Angelini S. Clinical relevance of circulating molecules in cancer: focus on gastrointestinal stromal tumors. Ther Adv Med Oncol. 2019 Mar 1;11:1758835919831902.
  • Serrano-Candelas E, Ainsua-Enrich E, Navinés-Ferrer A, Rodrigues P, García-Valverde A, Bazzocco S, Macaya I, Arribas J, Serrano C, Sayós J, Arango D, Martin M. Silencing of adaptor protein SH3BP2 reduces KIT/PDGFRA receptors expression and impairs gastrointestinal stromal tumors growth. Mol Oncol. 2018 Aug;12(8):1383-1397.
  • Moura DS, Ramos R, Fernandez-Serra A, Serrano T, Cruz J, Alvarez-Alegret R, Ortiz-Duran R, Vicioso L, Gomez-Dorronsoro ML, Garcia Del Muro X, Martinez-Trufero J, Rubio-Casadevall J, Sevilla I, Lainez N, Gutierrez A, Serrano C, Lopez-Alvarez M, Hindi N, Taron M, López-Guerrero JA, Martin-Broto J. Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients. Oncotarget. 2018 Apr 3;9(25):17576-17588.
  • George S, Serrano C, Hensley ML, Ray-Coquard I. Soft Tissue and Uterine Leiomyosarcoma. J Clin Oncol. 2018 Jan 10;36(2):144-150.
  • Serrano C, George S, Valverde C, Olivares D, García-Valverde A, Suárez C, Morales-Barrera R, Carles J. Novel Insights into the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors. Target Oncol. 2017 Jun;12(3):277-288.
  • Poveda A, García Del Muro X, López-Guerrero JA, Cubedo R, Martínez V, Romero I, Serrano C, Valverde C, Martín-Broto J; GEIS (Grupo Español de Investigación en Sarcomas/Spanish Group for Sarcoma Research). GEIS guidelines for gastrointestinal sarcomas (GIST). Cancer Treat Rev. 2017 Apr;55:107-119.
  • Martin-Broto J, Martinez-Marín V, Serrano C, Hindi N, López-Guerrero JA, Bisculoa M, Ramos-Asensio R, Vallejo-Benítez A, Marcilla-Plaza D, González-Cámpora R. Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis. Clin Transl Oncol. 2017 May;19(5):536-545.
  • Poveda A, Martinez V, Serrano C, Sevilla I, Lecumberri MJ, de Beveridge RD, Estival A, Vicente D, Rubió J, Martin-Broto J. SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016). Clin Transl Oncol. 2016 Dec;18(12):1221-1228.
  • Serrano C, Romagosa C, Hernández-Losa J, Simonetti S, Valverde C, Moliné T, Somoza R, Pérez M, Vélez R, Vergés R, Domínguez R, Carles J, Ramón Y Cajal S. RAS/MAPK pathway hyperactivation determines poor prognosis in undifferentiated pleomorphic sarcomas. Cancer. 2016 Jan 1;122(1):99-107.
  • Garner AP, Gozgit JM, Anjum R, Vodala S, Schrock A, Zhou T, Serrano C, Eilers G, Zhu M, Ketzer J, Wardwell S, Ning Y, Song Y, Kohlmann A, Wang F, Clackson T, Heinrich MC, Fletcher JA, Bauer S, Rivera VM. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014 Nov 15;20(22):5745-5755.
  • George S, Barysauskas C, Serrano C, Oduyebo T, Rauh-Hain JA, Del Carmen MG, Demetri GD, Muto MG. Retrospective cohort study evaluating the impact of intraperitoneal morcellation on outcomes of localized uterine leiomyosarcoma. Cancer. 2014 Oct 15;120(20):3154-8.
  • Serrano C, George S. Recent advances in the treatment of gastrointestinal stromal tumors. her Adv Med Oncol. 2014 May;6(3):115-27.
  • Serrano C, Wang Y, Mariño-Enríquez A, Lee JC, Ravegnini G, Morgan JA, Bertagnolli MM, Beadling C, Demetri GD, Corless CL, Heinrich MC, Fletcher JA. KRAS and KIT Gatekeeper Mutations Confer Polyclonal Primary Imatinib Resistance in GI Stromal Tumors: Relevance of Concomitant Phosphatidylinositol 3-Kinase/AKT Dysregulation. J Clin Oncol. 2015 Aug 1;33(22):e93-6.
  • Serrano C, Nucci MR, Tirumani SH, Raut CP, George S. Hormone dependency in metastatic low-grade leiomyosarcoma following uterine smooth muscle tumour of uncertain malignant potential. BMJ Case Rep. 2014 Mar 27;2014.
  • Simonetti S, Serrano C, Hernández-Losa J, Bagué S, Orellana R, Valverde C, Lleonart ME, Aizpurua M, Carles J, Ramón y Cajal S, Romagosa C. Schwannomas, benign tumors with a senescent phenotype. Histol Histopathol. 2014 Jun;29(6):721-30.
  • Serrano C, George S. Leiomyosarcoma. Hematol Oncol Clin North Am. 2013 Oct;27(5):957-74.
  • Serrano C, Simonetti S, Hernández-Losa J, Valverde C, Carrato C, Bagué S, Orellana R, Somoza R, Moliné T, Carles J, Huguet P, Romagosa C, Ramón y Cajal S. BRAF V600E and KRAS G12S mutations in peripheral nerve sheath tumours. Histopathology. 2013 Feb;62(3):499-504.
  • Morales-Barrera R, Bellmunt J, Suárez C, Valverde C, Guix M, Serrano C, Gallén M, Carles J. Cisplatin and gemcitabine administered every two weeks in patients with locally advanced or metastatic urothelial carcinoma and impaired renal function. Eur J Cancer. 2012 Aug;48(12):1816-21.
  • Serrano C, Morales R, Suárez C, Núñez I, Valverde C, Rodón J, Humbert J, Padrós O, Carles J. Emerging therapies for urothelial cancer. Cancer Treat Rev. 2012 Jun;38(4):311-7.
  • Serrano C, Cortés J, De Mattos-Arruda L, Bellet M, Gómez P, Saura C, Pérez J, Vidal M, Muñoz-Couselo E, Carreras MJ, Sánchez-Ollé G, Tabernero J, Baselga J, Di Cosimo S. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2012 Apr;23(4):897-902.
  • Serrano C, Alonso J, Gómez-Mariano G, Aguirre E, Diez O, Gadea N, Bosch N, Balmaña J, Graña B. Low penetrance hereditary retinoblastoma in a family: what should we consider in the genetic counselling process and follow up? Fam Cancer. 2011 Sep;10(3):617-21.
  • Cedrés S, Quispe I, Martínez P, Longo M, Rodríguez E, Serrano C, Muñoz E, Pallisa E, Felip E. Computed tomography (CT) predicts accurately the pathologic tumour size in stage I non-small-cell lung cancer (NSCLC). Clin Transl Oncol. 2010 Dec;12(12):829-35.
  • Serrano C, García Á, Brana I, Pérez-Benavente A, Oaknin A. Angiosarcoma of the ovary: is it always a lethal disease? J Clin Oncol. 2010 Nov 20;28(33):e675-7.
  • Serrano C, Markman B, Tabernero J. Integration of anti-epidermal growth factor receptor therapies with cytotoxic chemotherapy. Cancer J. 2010 May-Jun;16(3):226-34.
  • Serrano C, Suárez C, Andreu J, Carles J. Acute aortic dissection during sorafenib-containing therapy. Ann Oncol. 2010 Jan;21(1):181-2.
  • Prat A, Serrano C, Valverde C, Calvo E. Acute severe hypothyroidism induced by sunitinib. Radiother Oncol. 2008 Oct;89(1):124-5.
  • Prat A, Martínez P, Serrano C, Montero MA, Andreu J, Cortés J. Acute lung injury associated with docetaxel and bevacizumab. Clin Oncol (R Coll Radiol). 2007 Dec;19(10):803-5.
  • Serrano C, Mackintosh C, Herrero D, Martins AS, de Alava E, Hernández T, Pérez-Fontán J, Abad M, Pérez A, Serrano E, Bullón A, Orfao A. Imatinib is not a potential alternative treatment for uterine leiomyosarcoma. Clin Cancer Res. 2005 Jul 1;11(13):4977-9.

Projects

  1. Genomic determinants of tumor evolution and progression in sarcomas with simple karyotype – Fundación CRIS – 1/05/2024-30/04/2029 – PI: César Serrano
  2. Centralization of pathological diagnosis and implementation of precision medicine strategies in sarcomas. Asociación Española Contra el Cáncer – AECC (Spanish Association against Cancer). 2023-2026.
  3. Determinantes clínicos y moleculares de respuesta y progresión a la inhibición de KIT en pacientes con tumores del estroma gastrointestinal (GIST) con respuesta prolongada a Imatinib. Grupo Español de Investigación en Sarcomas – GEIS (Spanish Group of Sarcoma Research). 2017-2022.
  4. Determinantes clínicos y moleculares de respuesta y progresión a la inhibición de KIT en pacientes con tumores del estroma gastrointestinal (GIST) con respuesta prolongada a Imatinib. Grupo Español de Investigación en Sarcomas (GEIS), Sociedad Española de Oncología Médica (SEOM), and Fundación Mari Paz Jiménez Casado. 2022-2025.
  5. Modulating our ubiquitination machinery to innovate treatments and drug discovery in cancer. Asociación Española Contra el Cáncer– AECC (Spanish Association against Cancer). 2021-2024.
  6. Estudio de los mecanismos de resistencia a la terapia personalizada (inhibidores KIT/PDGFRA) en tumores gastrointestinales de estroma (GIST). Fundación FERO (FERO Foundation). 2020-2022.
  7. Estudio de los mecanismos de resistencia a la terapia personalizada (inhibidores KIT/PDGFRA) en tumores gastrointestinales de estroma  (GIST). Fundación FERO (FERO Foundation). 2020-2023.
  8. DIVAS-Dissecting VAsculas Sarcomas. Grupo Español de Investigación en Sarcomas – GEIS (Spanish Group of Sarcoma Research). 2020-2022.
  9. DIVAS-Dissecting VAsculas Sarcomas. Grupo Español de Investigación en Sarcomas – GEIS (Spanish Group of Sarcoma Research). 2020-2023.
  10. Perfiles de resistencia molecular a la inhibición de KIT/PDGFRA en tumores del estroma gastrointestinal. Asociación Española Contra el Cáncer – AECC (Spanish Association against Cancer). 2020-2024.
  11. Caracterización del potencial predictivo y terapéutico del FBXO32 como mediador crítico de la señalización oncogénica de KIT/PDGFRA en tumores del estroma gastrointestinal. Fundación Mari Paz Jiménez Casado – FMPJC. 2017-2022.
  12. Estudio de los determinantes bioloógicos responsables de respuesta prolongada (>5 años) a la inhibición de KIT en tumores del estroma gastrointestinal (GIST). Sociedad Española de Oncología Médica – SEOM (Spanish Society of Medical Oncology). 2018-2022.
  13. Start-up – Estudio de los mecanismos de resistencia a la terapia personalizada (inhibidores KIT/PDGFRA) en tumores gastrointestinales de estroma (GIST). Fundación FERO (FERO Foundation). 2021-2022.

Project Funding

The Sarcoma Translational Research Group receives support from the FERO Foundation through a Start-Up grant for the creation and consolidation of the group in the VHIO.

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