Manuel Hidalgo

Hospital Universitario Madrid Sanchinarro, Madrid, Madrid, Spain

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Publications (230)1815.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BRAF V600 mutations occur in various nonmelanoma cancers. We undertook a histology-independent phase 2 "basket" study of vemurafenib in BRAF V600 mutation-positive nonmelanoma cancers. We enrolled patients in six prespecified cancer cohorts; patients with all other tumor types were enrolled in a seventh cohort. A total of 122 patients with BRAF V600 mutation-positive cancer were treated, including 27 patients with colorectal cancer who received vemurafenib and cetuximab. The primary end point was the response rate; secondary end points included progression-free and overall survival. In the cohort with non-small-cell lung cancer, the response rate was 42% (95% confidence interval [CI], 20 to 67) and median progression-free survival was 7.3 months (95% CI, 3.5 to 10.8). In the cohort with Erdheim-Chester disease or Langerhans'-cell histiocytosis, the response rate was 43% (95% CI, 18 to 71); the median treatment duration was 5.9 months (range, 0.6 to 18.6), and no patients had disease progression during therapy. There were anecdotal responses among patients with pleomorphic xanthoastrocytoma, anaplastic thyroid cancer, cholangiocarcinoma, salivary-duct cancer, ovarian cancer, and clear-cell sarcoma and among patients with colorectal cancer who received vemurafenib and cetuximab. Safety was similar to that in prior studies of vemurafenib for melanoma. BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis. The histologic context is an important determinant of response in BRAF V600-mutated cancers. (Funded by F. Hoffmann-La Roche/Genentech; number, NCT01524978.).
    New England Journal of Medicine 08/2015; 373(8):726-36. DOI:10.1056/NEJMoa1502309 · 55.87 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):1493-1493. DOI:10.1158/1538-7445.AM2015-1493 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):2315-2315. DOI:10.1158/1538-7445.AM2015-2315 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):CT110-CT110. DOI:10.1158/1538-7445.AM2015-CT110 · 9.33 Impact Factor
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    ABSTRACT: nab-Paclitaxel plus gemcitabine was superior to gemcitabine alone for patients with metastatic pancreatic cancer (MPC) in the phase III MPACT trial. This study evaluated the association of Secreted Protein Acidic and Rich in Cysteine (SPARC) levels with efficacy as an exploratory endpoint. Patients with previously untreated MPC (N = 861) received nab-paclitaxel plus gemcitabine or gemcitabine alone. Baseline SPARC level was measured in the tumor stroma and epithelia (archival biopsies) and plasma. Experiments were performed in PC mouse models in which SPARC was intact or deleted. SPARC was measured in the tumor stroma of 256 patients (30%), the tumor epithelia of 301 patients (35%), and plasma of 343 patients (40%). Stroma-evaluable samples were from metastases (71%), the pancreas (11%), or of unidentifiable origin (insufficient tissue to determine; 17%). For all patients, stromal SPARC level (high [n = 71] vs. low [n = 185]) was not associated with overall survival (OS; hazard ratio 1.019; P = 0.903); multivariate analysis confirmed this lack of association. There was no association between stromal SPARC level and OS in either treatment arm. Neither tumor epithelial SPARC nor plasma SPARC were associated with OS. Results from a SPARC knockout mouse model treated with nab-paclitaxel plus gemcitabine revealed no correlation between SPARC expression and tumor progression or treatment efficacy. SPARC levels were not associated with efficacy in patients with MPC. This exploratory analysis does not support making treatment decisions regarding nab-paclitaxel plus gemcitabine or gemcitabine alone in MPC based on SPARC expression. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 07/2015; DOI:10.1158/1078-0432.CCR-14-3222 · 8.72 Impact Factor
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    ABSTRACT: A current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for the study of human tumors. Here we report the development of a humanized murine model that can be used to analyze the pharmacodynamics and antitumor properties of immunostimulatory monoclonal antibodies (mAb), in settings where the receptors targeted by the mAbs are expressed. Human lymphocytes transferred into immunodeficient mice underwent activation and redistributed to murine organs, where they exhibited cell surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations resulted in a lethal CD4+ T cell-mediated disease (xenograft-versus-host disease), which was aggravated when murine subjects were administered clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab). In mice engrafted with human colorectal HT-29 carcinoma cells and allogeneic human PBMCs, or with a patient-derived gastric carcinoma and peripheral blood mononuclear cells from the same patient, we found that co-administration of urelumab and nivolumab was sufficient to significantly slow tumor growth. Correlated with this result were increased numbers of activated human T lymphocytes producing IFNγ and decreased numbers of human regulatory T lymphocytes in the tumor xenografts, possibly explaining the efficacy of the therapeutic regimen. Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; 75(15 Supplement). DOI:10.1158/0008-5472.CAN-14-3510 · 9.33 Impact Factor
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    ABSTRACT: The "Warburg effect" describes a peculiar metabolic feature of many solid tumors, namely their high glycolytic activity for biosynthesis and an inefficient generation of ATP. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small molecule inhibition in cancer cells. In this study, we used FX11, a small molecule inhibitor of LDH-A, to investigate this possible vulnerability in a panel of 15 patient-derived mouse xenograft (PDX) models of pancreatic cancer. Unexpectedly, the p53 status of the PDX tumor determined the response to FX11. Tumors harboring wild-type (WT) TP53 were completely resistant to FX11. In contrast, tumors harboring mutant TP53 exhibited increased apoptosis, reduced proliferation indices and attenuated tumor growth when exposed to FX11. [18F]-FDG PET-CT scans revealed a relative increase in glucose uptake in mutant TP53 versus WT TP53 tumors, with FX11 administration downregulating metabolic activity only in mutant TP53 tumors. Through a non-invasive quantitative assessment of lactate production, as determined by 13C magnetic resonance spectroscopy (MRS) of hyperpolarized pyruvate, we confirmed that FX11 administration inhibited pyruvate-to-lactate conversion only in mutant TP53 tumors, a feature associated with reduced expression of the TP53 target gene TIGAR, which is known to regulate glycolysis. Taken together, our findings highlight p53 status in pancreatic cancer as biomarker to predict sensitivity to LDH-A inhibition, with regard to both real-time non-invasive imaging by 13C MRS as well as therapeutic response. Copyright © 2015, American Association for Cancer Research.
    Cancer Research 06/2015; 75(16). DOI:10.1158/0008-5472.CAN-15-0108 · 9.33 Impact Factor
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    ABSTRACT: The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-dependent HER dimer signaling. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of MEHD7945A. Patients with locally advanced or metastatic epithelial tumors received escalating doses of MEHD7945A (1-30 mg/kg) every 2 weeks (q2w) until disease progression or intolerable toxicity. An expansion cohort was enrolled at the recommended phase II dose (14 mg/kg, q2w). Plasma samples, tumor biopsies, FDG-PET were obtained for assessment of pharmacokinetics, and pharmacodynamic modulation downstream of EGFR and HER3. No dose-limiting toxicities or MEHD7945A-related grade ≥ 4 adverse events (AE) were reported in dose-escalation (n = 30) or expansion (n = 36) cohorts. Related grade 3 AEs were limited to diarrhea and nausea in the same patient (30 mg/kg). Related AEs in ≥20% of patients ≤24 hours after the first infusion included grade 1/2 headache, fever, and chills, which were managed with premedication and/or symptomatic treatment. Pharmacodynamic data indicated target inhibition in 25% of evaluable patients. Best response by RECIST included 2 confirmed partial responses in squamous cell carcinomas of head and neck (SCCHN) patients with high tumor tissue levels of the HER3 ligand heregulin; 14 patients had stable disease ≥8 weeks, including SCCHN (n = 3), colorectal cancer (n = 6), and non-small cell lung cancer (n = 3). MEHD7945A was well-tolerated as single agent with evidence of tumor pharmacodynamic modulation and antitumor activity in SCCHN. Phase II studies were initiated with flat (nonweight-based) dosing at 1,100 mg q2w in SCCHN and colorectal cancer. Clin Cancer Res; 21(11); 2462-70. ©2015 AACR. ©2015 American Association for Cancer Research.
    Clinical Cancer Research 06/2015; 21(11):2462-70. DOI:10.1158/1078-0432.CCR-14-2412 · 8.72 Impact Factor
  • Pancreatology 06/2015; 15(3):S125. DOI:10.1016/j.pan.2015.05.441 · 2.84 Impact Factor
  • Pancreatology 06/2015; 15(3):S124-S125. DOI:10.1016/j.pan.2015.05.439 · 2.84 Impact Factor
  • Samuel Aparicio · Manuel Hidalgo · Andrew L Kung
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    ABSTRACT: Patient-derived xenograft (PDX) models are now being widely used in cancer research and have the potential to greatly inform our understanding of cancer biology. However, many questions remain, especially regarding the ability of PDX models to affect clinical decision making. With these points in mind, we asked three scientists to give their opinions on the generation and uses of PDX models and the future of this field.
    Nature Reviews Cancer 04/2015; 15(5):311-6. DOI:10.1038/nrc3944 · 37.40 Impact Factor
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    ABSTRACT: The primary objective of this phase I study of LY2780301, a dual p70 S6 kinase and Akt inhibitor, was to determine the recommended phase II dose as a single agent in patients with advanced cancer. Secondary objectives included safety, pharmacokinetic, and pharmacodynamic analyses, and co-clinical analyses in Avatar models. Eligible patients received total daily doses of LY2780301 100-500 mg, given orally as a single dose or divided into 2 doses for 28-day cycles. Dose escalation followed 3 + 3 design. The primary pharmacodynamic endpoint was inhibition of S6 assessed by skin and tumor biopsy. Thirty-two patients were treated. Common toxicities possibly related to treatment included constipation (19 %), fatigue (13 %), nausea (9 %), and diarrhea (9 %). Grade 3/4 toxicities potentially related to treatment were anemia (n = 2), increased alanine aminotransferase/aspartate aminotransferase (ALT) (n = 1), and increased gamma-glutamyl transpeptidase (GGT) (n = 1). One patient experienced best overall response of prolonged stable disease for 6 cycles. Plasma exposures of LY2780301 exceeded predicted efficacious exposures, but were not dose proportional. Among patients receiving 500 mg daily >50 % exhibited reduced S6 in skin biopsies at Day 8 of treatment, but the effect was not maintained. Plasma concentrations of LY2780301 and/or its metabolites were not correlated with S6 expression in the epidermis. There was minimal antitumor activity against the model, CRC 019. Avatar models showed minimal pharmacodynamic effects consistent with the observed antitumor effects. This study suggests a dose of LY2780301 500 mg QD for future studies.
    Investigational New Drugs 04/2015; 33(3). DOI:10.1007/s10637-015-0241-7 · 2.92 Impact Factor
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    ABSTRACT: Cancer stem cells (CSCs) represent the root of many solid cancers including pancreatic ductal adenocarcinoma, are highly chemoresistant and represent the cellular source for disease relapse. However the mechanisms involved in these processes still need to be fully elucidated. Understanding the mechanisms implicated in chemoresistance and metastasis of pancreatic cancer is critical to improving patient outcomes. Micro-RNA (miRNA) expression analyses were performed to identify functionally defining epigenetic signatures in pancreatic CSC-enriched sphere-derived cells and gemcitabine-resistant pancreatic CSCs. We found the miR-17-92 cluster to be downregulated in chemoresistant CSCs versus non-CSCs and demonstrate its crucial relevance for CSC biology. In particular, overexpression of miR-17-92 reduced CSC self-renewal capacity, in vivo tumourigenicity and chemoresistance by targeting multiple NODAL/ACTIVIN/TGF-β1 signalling cascade members as well as directly inhibiting the downstream targets p21, p57 and TBX3. Overexpression of miR-17-92 translated into increased CSC proliferation and their eventual exhaustion via downregulation of p21 and p57. Finally, the translational impact of our findings could be confirmed in preclinical models for pancreatic cancer. Our findings therefore identify the miR-17-92 cluster as a functionally determining family of miRNAs in CSCs, and highlight the putative potential of developing modulators of this cluster to overcome drug resistance in pancreatic CSCs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Gut 04/2015; DOI:10.1136/gutjnl-2014-308470 · 14.66 Impact Factor
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    ABSTRACT: Colorectal cancer is a major health problem and the second cause of cancer related death in western countries. Signaling pathways that control tissue homeostasis are often deregulated during tumorigenesis and contribute to tumor development. Studies in mouse models have shown that the p38 MAPK pathway regulates homeostasis in colon epithelial cells but also plays an important role in colon tumor maintenance. In this study, we have investigated the role of p38 MAPK signaling in patient-derived xenografts (PDXs) from three different human colon tumors representing clinical heterogeneity and that recapitulate the human tumor conditions both at histological and molecular levels. We have found that PH797804, a chemical inhibitor of p38 MAPK, reduces tumor growth of the three PDXs, which correlates with impaired colon tumor cell proliferation and survival. The inhibition of p38 MAPK in PDXs results in downregulation of the IL-6/STAT3 signaling pathway, which is a key regulator of colon tumorigenesis. Our results show the importance of p38 MAPK in human colon tumor growth using a preclinical model, and support that inhibition of p38 MAPK signaling may have therapeutic interest for colon cancer treatment.
    Oncotarget 04/2015; 6(11). DOI:10.18632/oncotarget.3816 · 6.36 Impact Factor
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    ABSTRACT: Objectives: The tumour stroma/microenvironment not only provides structural support for tumour development, but more importantly it provides cues to cancer stem cells (CSCs) that regulate their self-renewal and metastatic potential. This is certainly true for pancreatic ductal adenocarcinomas (PDAC), where tumour-associated fibroblasts, pancreatic stellate cells and immune cells create an abundant paracrine niche for CSCs via microenvironment-secreted factors. Thus understanding the role that tumour stroma cells play in PDAC development and CSC biology is of utmost importance. Design: Microarray analyses, tumour microarray immunohistochemical assays, in vitro co-culture experiments, recombinant protein treatment approaches and in vivo intervention studies were performed to understand the role that the immunomodulatory cationic antimicrobial peptide 18/LL-37 (hCAP-18/LL-37) plays in PDAC biology. Results: We found that hCAP-18/LL-37 was strongly expressed in the stroma of advanced primary and secondary PDAC tumours and is secreted by immune cells of the stroma (eg, tumour-associated macrophages) in response to tumour growth factor-β1 and particularly CSC-secreted Nodal/ActivinA. Treatment of pancreatic CSCs with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumourigenicity via formyl peptide receptor 2 (FPR2)- and P2X purinoceptor 7 receptor (P2X7R)-dependent mechanisms, which could be reversed by inhibiting these receptors. Importantly, in a genetically engineered mouse model of K-Ras-driven pancreatic tumourigenesis, we also showed that tumour formation was inhibited by either reconstituting these mice with bone marrow from cathelicidin-related antimicrobial peptide (ie, murine homologue of hCAP-18/LL-37) knockout mice or by pharmacologically inhibiting FPR2 and P2X7R. Conclusions: Thus, hCAP-18/LL-37 represents a previously unrecognised PDAC microenvironment factor that plays a critical role in pancreatic CSC-mediated tumourigenesis.
    Gut 04/2015; 53(08). DOI:10.1136/gutjnl-2014-308935 · 14.66 Impact Factor
  • Ignacio Garrido-Laguna · Manuel Hidalgo
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    ABSTRACT: Pancreatic cancer is expected to be the second deadliest malignancy in the USA by 2020. The survival rates for patients with other gastrointestinal malignancies have increased consistently during the past 30 years; unfortunately, however, the outcomes of patients with pancreatic cancer have not changed significantly. Although surgery remains the only curative treatment for pancreatic cancer, therapeutic strategies based on initial resection have not substantially improved the survival of patients with resectable disease over the past 25 years; presently, more than 80% of patients suffer disease relapse after resection. Preclinical evidence that pancreatic cancer is a systemic disease suggests a possible benefit for early administration of systemic therapy in these patients. In locally advanced disease, the role of chemoradiotherapy is increasingly being questioned, particularly considering the results of the LAP-07 trial. Novel biomarkers are clearly needed to identify subsets of patients likely to benefit from chemoradiotherapy. In the metastatic setting, FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin), and nab-paclitaxel plus gemcitabine have yielded only modest improvements in survival. Thus, new treatments are urgently needed for patients with pancreatic cancer. Herein, we review the state-of-the-art of pancreatic cancer treatment, and the upcoming novel therapeutics that hold promise in this disease are also discussed.
    Nature Reviews Clinical Oncology 03/2015; 12(6). DOI:10.1038/nrclinonc.2015.53 · 14.18 Impact Factor
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    ABSTRACT: Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a cancer of the exocrine pancreas with unmet medical need and is strongly promoted by tumor-associated macrophages (TAMs). The presence of TAMs is associated with poor clinical outcome and their overall role therefore appears to be pro-tumorigenic. The "don't eat me" signal CD47 on cancer cells communicates to the signal regulatory protein-α on macrophages and prevents their phagocytosis. Thus, inhibition of CD47 may offer a new opportunity to turn TAMs against PDAC cells including cancer stem cells (CSCs) as the exclusively tumorigenic population. Experimental Design: We studied in vitro and in vivo the effects of CD47 inhibition on CSCs using a large set of primary pancreatic cancer (stem) cells as well as xenografts of primary human PDAC tissue. Results: CD47 was highly expressed on CSCs, but not on other non-malignant cells in the pancreas. Targeting CD47 efficiently enhanced phagocytosis of a representative set of primary human pancreatic cancer (stem) cells and, even more intriguingly, also directly induced their apoptosis in the absence of macrophages during long-term inhibition of CD47. In patient-derived xenografts models, CD47 targeting alone did not result in relevant slowing of tumor growth, but the addition of Gemcitabine or Abraxane resulted in sustained tumor regression and prevention of disease relapse long after discontinuation of treatment. Conclusions: These data are consistent with efficient in vivo targeting of CSCs and strongly suggest that CD47 inhibition could be a novel adjuvant treatment strategy for PDAC independent of underlying and highly variable driver mutations. Copyright © 2015, American Association for Cancer Research.
    Clinical Cancer Research 02/2015; DOI:10.1158/1078-0432.CCR-14-1399 · 8.72 Impact Factor
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    ABSTRACT: Purpose: This first-in-human study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of single and multiple doses of TAK-441, an investigational inhibitor of the Hedgehog signaling pathway. Experimental Design: Patients with advanced, solid tumors received daily oral TAK-441 (50-1600 mg/day); daily dose was doubled in each subsequent cohort until the maximum tolerated/feasible dose (MTD/MFD) was reached. Blood was collected to evaluate TAK-441 plasma concentrations. Skin biopsies were obtained to evaluate suppression of the Hedgehog-regulated gene Gli1. Results: Thirty-four patients were enrolled (median age 59). The most common diagnoses were colorectal cancer (26%), basal cell carcinoma (BCC, 21%), and pancreatic cancer (9%). The MFD of 1600 mg/day (based on tablet size and strength) was considered the MTD. Dose-limiting toxicities included muscle spasms and fatigue. Grade ≥3 treatment-emergent adverse events, regardless of causality, occurred in 15 patients (44%), of which hyponatremia (n=4) and fatigue (n=3) were most common. Oral absorption was fairly rapid; median Tmax was 2.0-4.0 hours after a single dose. Mean elimination half-life was 13.5-22.6 hours. Systemic exposure of TAK-441 based on the area under the plasma concentration-time curve was linear across the dose range. Gli1 expression in skin biopsies was strongly inhibited at all dose levels. Best response was partial response (1 patient with BCC) and stable disease (7 patients with various solid tumors). Conclusion: TAK-441 was generally well tolerated up to MFD of 1600 mg/day, with preliminary antitumor activity. Further study of TAK-441 may be appropriate in populations selected for tumors with ligand-dependent or independent Hedgehog signaling. Copyright © 2014, American Association for Cancer Research.
    Clinical Cancer Research 12/2014; 21(5). DOI:10.1158/1078-0432.CCR-14-1234 · 8.72 Impact Factor
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    ABSTRACT: In a personalized treatment designed for a patient with pancreatic cancer resistant to other treatments, the success of Mitomycin C (MMC) has been highlighted. This was revealed in a murine xenograft tumor model encompassing pancreatic adenocarcinoma cells extracted from the patient. The patient was found to exhibit a biallelic inactivation of the PALB2 gene, involved in DNA repair in addition to another mutation in the TSC2 gene that induces susceptibility of the tumor to therapeutic targets of the PI3K-mTOR pathway. The aim of the study was to apply metabolomics to elucidate the modes of action of each therapy, suggesting why MMC was so successful in this patient and why it could be a more popular choice in future pancreatic cancer treatment. The effectiveness of MMC compared to rapamycin (RM), another relevant therapeutic agent has been evaluated through liquid- and gas-chromatography mass spectrometry-based metabolomic analyses of the xenograft tumors. The relative concentrations of many metabolites in the xenograft tumors were found to be increased by MMC relative to other treatments (RM and a combination of both), including a number that are involved in central carbon metabolism (CCM). Metabolic fingerprinting revealed statistically significantly altered pathways including, but not restricted to, the pentose phosphate pathway, glycolysis, TCA cycle, purine metabolism, fatty acid biosynthesis, in addition to many significant lipid and amino acid alterations. Given the genetic background of the patient, it was expected that the combined therapy would be most effective; however, the most effective was MMC alone. It is proposed that the effectiveness of MMC is owed to its direct effect on CCM, a vital region of tumor metabolism.
    12/2014; 2(6). DOI:10.1002/prp2.67
  • Nature Medicine 11/2014; 20(11):1230-1231. DOI:10.1038/nm.3701 · 27.36 Impact Factor

Publication Stats

13k Citations
1,815.65 Total Impact Points


  • 2009–2015
    • Hospital Universitario Madrid Sanchinarro
      Madrid, Madrid, Spain
    • Centro Nacional de Investigaciones Oncológicas
      • Clinical Research Programme
      Madrid, Madrid, Spain
  • 2010–2014
    • University Foundation San Pablo CEU
      • Faculty of Medicine
      Madrid, Madrid, Spain
  • 2013
    • Hospital Carlos III - Madrid
      Madrid, Madrid, Spain
    • Complutense University of Madrid
      Madrid, Madrid, Spain
  • 2002–2013
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • The Ohio State University
      • Division of Hematology
      Columbus, Ohio, United States
  • 2012
    • Hospital Clínico San Carlos
      • Servicio de Oncología Médica
      Madrid, Madrid, Spain
  • 2004–2012
    • Johns Hopkins Medicine
      • Department of Pathology
      Baltimore, Maryland, United States
    • Beth Israel Deaconess Medical Center
      • Division of Hematology/Oncology
      Boston, Massachusetts, United States
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2008–2011
    • Hospital Universitario 12 de Octubre
      Madrid, Madrid, Spain
    • Hospital 12 de Octubre
      Madrid, Madrid, Spain
  • 1999–2009
    • University of Texas Health Science Center at San Antonio
      • • Department of Medicine
      • • Cancer Therapy & Research Center
      San Antonio, Texas, United States
  • 2006
    • Radiation Therapy and Cancer Institute
      San Juan, Texas, United States