El sarcoma inclou més de 70 entitats d’origen mesenquimàtic i constitueix entre l’1 i el 2 % de tots els càncers. Des d’una perspectiva biològica, els sarcomes poden classificar-se en dues grans categories: sarcomes genòmicament senzills impulsats per alteracions genètiques simples, com ara translocacions o mutacions activadores específiques, i tumors amb aberracions genòmiques complexes i desequilibrades. Cadascuna d’aquestes categories inclou diversos subtipus de sarcomes que sovint presenten profundes diferències en la seva composició molecular, el curs de la malaltia i l’enfocament terapèutic.
El nostre grup se centra en l’estudi dels sarcomes amb dependència oncogènica d’impulsors específics de la malaltia. Entre aquests, el tumor de l’estroma gastrointestinal (TEGI) és la neoplàsia maligna mesenquimatosa més freqüent i constitueix un model paradigmàtic per estudiar l’addicció als oncogens i identificar els mecanismes estructurals i funcionals de resposta i resistència als fàrmacs.
Els treballs en curs tenen com a objectiu aprofundir en la comprensió biològica del TEGI i altres sarcomes per avançar en el desenvolupament de fàrmacs. Un dels principals obstacles amb un impacte directe als resultats dels pacients té relació amb l’heterogeneïtat dels mecanismes de resistència. Per tant, el nostre objectiu general és identificar molècules i mecanismes de transducció de senyals crucials a la biologia del TEGI que puguin servir com a vulnerabilitats terapèutiques. La implicació de la via de la ubiquitina i els mecanismes de transducció de senyals de derivació s’han convertit els darrers anys en un dels principals focus d’atenció.
També duem a terme estudis genòmics i transcriptòmics d’alt rendiment per desxifrar els patrons evolutius de resistència a TEGI en el transcurs de la malaltia, i investiguem la biòpsia líquida en sarcoma per aportar proves sòlides que ajudin a orientar amb més precisió les decisions de tractament mitjançant seqüenciació plasmàtica. A més, el projecte GISTomics, una iniciativa europea impulsada pel nostre grup, vol avançar en el coneixement del panorama de l’evolució del TEGI. En la mateixa direcció, el nostre grup lidera iniciatives internacionals per investigar el paper de l’ADN tumoral circulant (ADNtc) als TEGI i altres sarcomes amb el doble objectiu d’obtenir informació sobre les característiques biològiques d’aquests tumors en pacients amb múltiples tractaments previs i determinar les principals vies per a la seva aplicació clínica.
A més del TEGI, el nostre grup ha iniciat noves línies de recerca centrades en altres subtipus de sarcoma, com els sarcomes d’origen muscular (leiomiosarcoma i rabdomiosarcoma), l’angiosarcoma i el liposarcoma. La medicina funcional de precisió és un dels principals focus de recerca en aquestes neoplàsies.
El nostre objectiu és tenir un veritable impacte clínic millorant el tractament i les cures diàries dels nostres pacients. Ens enorgulleix informar de la designació de la nostra Unitat Multidisciplinar de Sarcomes com a Centre Expert en Sarcomes de la Xarxa Europea de Referència ERN-EURACAN, per la qual cosa constitueix un entorn òptim per traduir els descobriments sobre el càncer en beneficis clínics.
- Identificació de mediadors moleculars crítics de la senyalització oncogènica en sarcomes.
- Caracterització dels mecanismes de resposta i resistència a les teràpies dirigides en sarcomes.
- Modelització preclínica i validació d’estratègies terapèutiques per traduir-les a escala clínica.
- Desenvolupament clínic de fàrmacs en sarcomes mitjançant assaigs clínics de fase I a fase III.
Figura: El tumor de l’estroma gastrointestinal (TEGI) és el tumor mesenquimàtic maligne més comú i un model exitós i paradigmàtic per disseccionar els mecanismes de resposta i resistència als agents dirigits molecularment. La recerca en curs del nostre grup està fent avançar aquest coneixement en dues direccions: en primer lloc, estem interrogant els mecanismes basats en mutacions que afecten la sensibilitat als inhibidors de KIT aprovats.
En segon lloc, estem investigant la progressió citogenètica que impulsa el creixement del TEGI. Aquests descobriments tenen un impacte directe en el futur del desenvolupament de fàrmacs en TEGI i altres malalties (figura de Serrano i George, Clin Cancer Res 2020; 26: 923-934).
Cap de grup
César Serrano
Oncòleg
Carlo M. Cicala
Becaris predoctorals
Alfonso García Valverde
Daniel Pilco Janeta
David Gómez Peregrina
Iván Olivares Rivas
Gemma Mur Bonet
Tècnic sènior
Jordi Rosell Aluja
Estudiant de postgrau
David Camell Raventós
Publicacions científiques més rellevants
- 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.
Totes les publicacions
- 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.
- 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.
- Modulating our ubiquitination machinery to innovate treatments and drug discovery in cancer . Asociación Española Contra el Cáncer– AECC (Spanish Association against Cancer). 2021-2024.
- 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.
- 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.
- 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.
- 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.
- DIVAS-Dissecting VAsculas Sarcomas. Grupo Español de Investigación en Sarcomas – GEIS (Spanish Group of Sarcoma Research). 2020-2022.
- 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.
- 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.
El Grup de Recerca Traslacional del Sarcoma rep el suport de la Fundació FERO a través d’un ajut Start-Up per a la creació i consolidació del grup al VHIO.
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