Phase I safety, pharmacokinetics, and inhibition of SRC activity study of saracatinib in patients with solid tumorsJose Baselga
Vall d Hebron Institute of Oncology, Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, Spain
Clin Cancer Res 16:4876-83. 2010
..Tumor biopsy samples were taken to investigate the effect of saracatinib on Src activity in tumors...
Novel anticancer targets: revisiting ERBB2 and discovering ERBB3Jose Baselga
Vall d Hebron Institute of Oncology, Vall d Hebron University Hospital, Passeig Vall d Hebron 119 129, Barcelona 08035, Spain
Nat Rev Cancer 9:463-75. 2009
..These new therapies include tyrosine kinase inhibitors, antibody-chemotherapy conjugates, heat-shock protein inhibitors and antibodies that interfere with the formation of ERBB2-ERBB3 dimers...
A major role of p95/611-CTF, a carboxy-terminal fragment of HER2, in the down-modulation of the estrogen receptor in HER2-positive breast cancersJosep Lluís Parra-Palau
Statistics Department, Faculty of Biology, Vall d Hebron Institute of Oncology, University of Barcelona, Barcelona, Spain
Cancer Res 70:8537-46. 2010
..2%). These results reveal a mechanism of ER regulation mediated by HER2, which suggests a new strategy to improve responses to endocrine therapy in breast cancer...
Clinical benefit of lapatinib-based therapy in patients with human epidermal growth factor receptor 2-positive breast tumors coexpressing the truncated p95HER2 receptorMaurizio Scaltriti
Department of Medical Oncology, Vall d Hebron University Hospital, Barcelona, Spain
Clin Cancer Res 16:2688-95. 2010
..We have studied the correlation between p95HER2 expression and response to lapatinib, both in preclinical models and in the clinical setting...
Expression of p95HER2, a truncated form of the HER2 receptor, and response to anti-HER2 therapies in breast cancerMaurizio Scaltriti
Medical Oncology Program, Medical Oncology Department, Vall d Hebron University Hospital and Research Institute, Barcelona 08035, Spain
J Natl Cancer Inst 99:628-38. 2007
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Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapyCelina García-García
Department of Experimental Therapeutics Laboratory, Vall d Hebron Institute of Oncology, Pg Vall d Hebron, Barcelona, Spain
Clin Cancer Res 18:2603-12. 2012
..The hypothesis is that the suppression of this pathway results in sensitization to anti-HER2 agents. However, this combinatorial strategy has not been comprehensively tested in models of trastuzumab and lapatinib resistance...
USP15 stabilizes TGF-β receptor I and promotes oncogenesis through the activation of TGF-β signaling in glioblastomaPieter J A Eichhorn
Vall d Hebron Institute of Oncology, Vall d Hebron University Hospital, Barcelona, Spain
Nat Med 18:429-35. 2012
..Our results show that USP15 regulates the TGF-β pathway and is a key factor in glioblastoma pathogenesis...
NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutationsVioleta Serra
Laboratory of Oncology Research, Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
Cancer Res 68:8022-30. 2008
..In summary, NVP-BEZ235 inhibits the PI3K/mTOR axis and results in antiproliferative and antitumoral activity in cancer cells with both wild-type and mutated p110-alpha...
A naturally occurring HER2 carboxy-terminal fragment promotes mammary tumor growth and metastasisKim Pedersen
Medical Oncology Research Program, Vall d Hebron University Hospital, Psg Vall d Hebron 119 129, 08035 Barcelona, Spain
Mol Cell Biol 29:3319-31. 2009
..These results demonstrate that 611-CTF is a potent oncogene capable of promoting mammary tumor progression and metastasis...
Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancerJose Baselga
Medical Oncology Service, Vall d Hebron University Hospital, P Vall d Hebron 119 129 08035 Barcelona, Spain
J Clin Oncol 23:5323-33. 2005
..To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer...
Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II studyJavier Cortes
Vall d Hebron University Hospital, Barcelona, Spain
Clin Cancer Res 15:307-14. 2009
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4E-binding protein 1, a cell signaling hallmark in breast cancer that correlates with pathologic grade and prognosisFederico Rojo
Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
Clin Cancer Res 13:81-9. 2007
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A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumorsFrancesco Atzori
Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
Clin Cancer Res 17:6304-12. 2011
..This study was designed to evaluate the safety and tolerability of dalotuzumab, determine the pharmacokinetic (PK) and pharmacodynamic (PD) profiles, and identify a recommended phase II dose...
ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cellsJudit Anido
Laboratory of Oncology Research, Medical Oncology Service, Vall d'Hebron University Hospital, Barcelona 08035, Spain
Clin Cancer Res 9:1274-83. 2003
..Our findings suggest that there is a strong rationale to conduct clinical trials of ZD1839 in patients with HER2-overexpressing breast tumors...
Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapyJose Baselga
Vall d Hebron Institute of Oncology, Vall d Hebron University Hospital, Paseo Vall d Hebron 119 129, Barcelona, Spain E 08035
J Clin Oncol 28:1138-44. 2010
..This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy...
Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patientsMaurizio Scaltriti
Departments of Medical Oncology and Molecular Pathology, Vall d Hebron Institute of Oncology, 08035 Barcelona, Spain
Proc Natl Acad Sci U S A 108:3761-6. 2011
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Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancerJose Baselga
Medical Oncology Department, Vall d Hebron University Hospital, P Vall d Hebron, Barcelona, Spain
J Clin Oncol 27:2630-7. 2009
..This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor, everolimus (RAD001)...
Phase II genomics study of ixabepilone as neoadjuvant treatment for breast cancerJose Baselga
Vall d Hebron University Hospital, Barcelona, Spain
J Clin Oncol 27:526-34. 2009
..Gene expression studies were undertaken using genes that were identified as potentially associated with sensitivity/resistance to ixabepilone in prior preclinical investigations...
Clinical surrogate markers of survival in advanced non-small cell lung cancer (NSCLC) patients treated with second-third line erlotinibSusana Cedres
Medical Oncology Service, Vall d Hebron University Hospital, Barcelona, Spain
Lung Cancer 66:257-61. 2009
..Inhibition of the EGFR pathway is a useful strategy in the treatment of patients with advanced NSCLC. The aim of this study is to assess predictive clinical parameters of efficacy...
Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose-escalation studyJosep Tabernero
Medical Oncology Department, Vall d Hebron University Hospital, P Vall d Hebron, 119 129, 08035 Barcelona, Spain
J Clin Oncol 28:1181-9. 2010
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HER2 carboxyl-terminal fragments regulate cell migration and cortactin phosphorylationJesús García-Castillo
Medical Oncology Research Program, Vall d Hebron University Hospital, Passeig Vall d Hebron 119 129, 08035 Barcelona, Spain
J Biol Chem 284:25302-13. 2009
..These results suggest that cortactin is a target of 611-CTF involved in the regulation of cell migration and, thus, in the metastatic behavior of breast tumors expressing this CTF...
Targeting tyrosine kinases in cancer: the second waveJose Baselga
Oncology Program, Vall d Hebron University Hospital and Vall d Hebron Research Institute, Universidad Autonoma de Barcelona, Barcelona 08035, Spain
Science 312:1175-8. 2006
..Agents directed against new molecular targets are also being explored...
Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamicsTeresa Macarulla
Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain
Mol Cancer Ther 9:2844-52. 2010
..Pharmacodynamic analyses in mitotic cells of both skin and tumor provided proof of mechanism for Aurora A kinase inhibition. A more potent, selective, second-generation Aurora A kinase inhibitor, MLN8237, is in clinical development...
Antitumor activity of the Hsp90 inhibitor IPI-504 in HER2-positive trastuzumab-resistant breast cancerMaurizio Scaltriti
Medical Oncology Department, Vall d Hebron Institute of Oncology, Barcelona, Spain
Mol Cancer Ther 10:817-24. 2011
..IPI-504-mediated Hsp90 inhibition may represent a novel therapeutic approach in trastuzumab refractory HER2-positive breast cancer...
4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implicationsGemma Armengol
Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
Cancer Res 67:7551-5. 2007
..Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets...
A phase I dose-escalating study of ES-285, a marine sphingolipid-derived compound, with repeat dose administration in patients with advanced solid tumorsEduardo Vilar
Department of Medical Oncology, Vall d Hebron University Hospital, Ps Vall d Hebron, 119 129, 08035 Barcelona, Spain
Invest New Drugs 30:299-305. 2012
..A phase I study was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), establish a safety profile, and to evaluate pharmacokinetics and efficacy of the drug...
Management of breast cancer with targeted agents: importance of heterogeneity. [corrected]Serena Di Cosimo
Breast Cancer Center, Medical Oncology Department, Vall d Hebron Institute of Oncology VHIO, Vall d Hebron University Hospital, 08035 Barcelona, Spain
Nat Rev Clin Oncol 7:139-47. 2010
..Thus, the overall management of breast cancer will increasingly require an understanding of breast cancer heterogeneicity, the biological nature of any given tumor as well the existence of increased personalized treatment options...
Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and nJose Baselga
Vall d Hebron University Hospital, Oncology Service, P Vall d Hebron 119 129, Barcelona 08035, Spain
J Clin Oncol 23:5568-77. 2005
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Phosphoinositide 3-kinase mutations in breast cancer: a "good" activating mutation?Serena Di Cosimo
Medical Oncology Department, Vall d Hebron Institute of Oncology VHIO, Vall d Hebron University Hospital, Barcelona, Spain
Clin Cancer Res 15:5017-9. 2009
..These findings will have to be considered in the design and interpretation of clinical trials with inhibitors of the PI3K pathway...
A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapyEnriqueta Felip
Medical Oncology Service and Pathology Service, Vall d Hebron University Hospital, Barcelona, Spain
Clin Cancer Res 14:3867-74. 2008
..To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy...
Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancerJose Baselga
Vall d Hebron University Hospital, Oncology Service, Barcelona, Spain
Oncologist 11:4-12. 2006
..Overall, results from clinical trials are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk:benefit ratio demonstrated in these studies...
Phosphorylated 4E binding protein 1: a hallmark of cell signaling that correlates with survival in ovarian cancerJosep Castellvi
Department of Pathology, Vall d Hebron University Hospital, Barcelona, Spain
Cancer 107:1801-11. 2006
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Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumorsJosep Tabernero
Medical Oncology Department, Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, corrected Barcelona, Spain
J Clin Oncol 26:1603-10. 2008
..In order to identify a rationally based dose and schedule for cancer treatment, we have conducted a tumor pharmacodynamic phase I study in patients with advanced solid tumors...
Targeted therapies in breast cancer: where are we now?Serena Di Cosimo
Medical Oncology Program, Medical Oncology Department, Vall d Hebron University Hospital, Passeig Vall d Hebron, Barcelona, Spain
Eur J Cancer 44:2781-90. 2008
..We will present these novel therapies and will analyse for each target the developmental status of some of the agents as well as target-specific challenges...
Epidermal growth factor receptor pathway inhibitorsJose Baselga
Medical Oncology Service, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Spain
Cancer Chemother Biol Response Modif 22:205-23. 2005
CLEOPATRA: a phase III evaluation of pertuzumab and trastuzumab for HER2-positive metastatic breast cancerJose Baselga
Vall d Hebron Institute of Oncology, Vall d Hebron University Hospital, Barcelona, Spain
Clin Breast Cancer 10:489-91. 2010
..Combining trastuzumab and pertuzumab therefore provides a more comprehensive blockade of the HER signaling pathways, resulting in greater antitumor efficacy...
Molecular prescreening to select patient population in early clinical trialsJordi Rodon
Medical Oncology Department, Vall d Hebron University Hospital, Spain
Nat Rev Clin Oncol 9:359-66. 2012
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Phase I pharmacokinetic/pharmacodynamic study of MLN8237, an investigational, oral, selective aurora a kinase inhibitor, in patients with advanced solid tumorsAndres Cervantes
Hematology and Medical Oncology Department, Hospital Clinico, INCLIVA, University of Valencia, Valencia, Spain
Clin Cancer Res 18:4764-74. 2012
..This phase I study investigated the safety, pharmacokinetics, and pharmacodynamics of MLN8237 (alisertib), an investigational, oral, selective AAK inhibitor, in 59 adults with advanced solid tumors...
Critical update and emerging trends in epidermal growth factor receptor targeting in cancerJose Baselga
Medical Oncology Service, Vall d Hebron Research Institute and Vall d Hebron University Hospital, Paseo Vall d Hebron 119 129, Barcelona 08035, Spain
J Clin Oncol 23:2445-59. 2005
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Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescencePier Davide Angelini
Preclinical Research, Vall d Hebron Institute of Oncology VHIO, Barcelona, Spain
Cancer Res 73:450-8. 2013
..Underscoring the functional relevance of the p95HER2-induced senescence secretome, we show that p95HER2-induced senescent cells promote metastasis in vivo in a non-cell-autonomous manner...
Targeting the microtubules in breast cancer beyond taxanes: the epothilonesJavier Cortes
Department of Oncology, Vall d Hebron University Hospital, Barcelona, Spain
Oncologist 12:271-80. 2007
..The results of these studies are eagerly awaited and it is anticipated that epothilones may become an important treatment option in patients with breast cancer...
Phase I pharmacokinetic and pharmacodynamic study of weekly 1-hour and 24-hour infusion BMS-214662, a farnesyltransferase inhibitor, in patients with advanced solid tumorsJosep Tabernero
Medical Oncology Department, Vall d Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain corrected
J Clin Oncol 23:2521-33. 2005
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TGF-beta signalling-related markers in cancer patients with bone metastasisJose Baselga
Vall d Hebron University Hospital, Barcelona, Spain
Biomarkers 13:217-36. 2008
..PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-beta inhibitor...
TGF-β Receptor Inhibitors Target the CD44(high)/Id1(high) Glioma-Initiating Cell Population in Human GlioblastomaJudit Anido
Vall d Hebron Institute of Oncology, Barcelona, Spain
Cancer Cell 18:655-68. 2010
..High CD44 and Id1 levels confer poor prognosis in GBM patients...
Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibitionJoan Albanell
Oncology Service, Vall d'Hebron University Hospital, Paseo Vall d'Hebron 119-129, Barcelona 08035, Spain
J Clin Oncol 20:110-24. 2002
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