Jose Perez-Garcia

Autonomous University of Barcelona, Cerdanyola del Vallès, Catalonia, Spain

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Publications (20)266.75 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of HER2 and development of trastuzumab pioneered the field of targeted therapy in breast cancer. Hoping to emulate the same clinical success, pharmaceutical companies have developed several antibodies against newly identified membrane-bound targets. Unfortunately, none of these agents has yet matched the thousands of lives saved by trastuzumab. In this article we review the most advanced therapeutic antibodies in breast cancer. While acknowledging their unquestionable benefit, we emphasize the need to better understand their biology and mechanisms of action in order to optimize their use in defined patient populations.
    Seminars in Oncology 07/2014; · 4.33 Impact Factor
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    ABSTRACT: Recent advances in breast cancer research have allowed deconstruction of the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in treatment options, including more personalized therapy and considerable improvements in patient outcomes. Although there are only a few targeted therapies approved for advanced breast cancer, several novel strategies targeting different tyrosine kinase receptors currently are under evaluation. Fibroblast growth factors and their receptors (FGFRs) are involved in different physiologic processes and also play a critical role in cancer cell proliferation and survival. This article focuses on the main molecular alterations of FGFRs, as well as the available preclinical and clinical data regarding FGFR inhibitors in breast cancer. In addition, we analyze the management of specific adverse events, such as hyperphosphatemia, and discuss unanswered questions regarding the clinical development of these agents.
    Current Breast Cancer Reports 06/2014; 6(2).
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    ABSTRACT: The fibroblast growth factor receptor (FGFR) cascade plays crucial roles in tumor cell proliferation, angiogenesis, migration and survival. Accumulating evidence suggests that in some tumor types, FGFRs are bona fide oncogenes to which cancer cells are addicted. Because FGFR inhibition can reduce proliferation and induce cell death in a variety of in vitro and in vivo tumor models harboring FGFR aberrations, a growing number of research groups have selected FGFRs as targets for anticancer drug development. Multikinase FGFR/vascular endothelial growth factor receptor (VEGFR) inhibitors have shown promising activity in breast cancer patients with FGFR1 and/or FGF3 amplification. Early clinical trials with selective FGFR inhibitors, which may overcome the toxicity constraints raised by multitarget kinase inhibition, are recruiting patients with known FGFR(1-4) status based on genomic screens. Preliminary signs of antitumor activity have been demonstrated in some tumor types, including squamous cell lung carcinomas. Rational combination of targeted therapies is expected to further increase the efficacy of selective FGFR inhibitors. Herein, we discuss unsolved questions in the clinical development of these agents and suggest guidelines for management of hyperphosphatemia, a class-specific mechanism-based toxicity. In addition, we propose standardized definitions for FGFR1 and FGFR2 gene amplification based on in situ hybridization methods. Extended access to next-generation sequencing platforms will facilitate the identification of diseases in which somatic FGFR(1-4) mutations, amplifications and fusions are potentially driving cancer cell viability, further strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors.
    Annals of Oncology 11/2013; · 7.38 Impact Factor
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    ABSTRACT: Translational and clinical cancer research, as well as clinical trials and treatment of cancer, are essentially structured based on the organ in which tumors originate. However, the recent explosion of knowledge about the molecular characteristics of tumors is opening a new way to tackle cancer. This article proposes a different approach to the classification of cancer with important implications for treatment and for basic, translational, and clinical research. The authors postulate that cancers from diverse organs of origin with similar molecular traits should be managed together. The common molecular features observed in different tumors determine clinical actions in a better way than organ-based classification. Thus, comparisons between tumors residing in different locations but with shared molecular characteristics will improve the therapeutic approach and the understanding of the biology of cancer. CA Cancer J Clin 2013. (©) 2013 American Cancer Society.
    CA A Cancer Journal for Clinicians 11/2013; · 153.46 Impact Factor
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    Jose Perez-Garcia, Eva Muñoz-Couselo, Javier Cortes
    EJC Supplements 09/2013; 11(2):254–256. · 2.71 Impact Factor
  • Jose Perez-Garcia, Javier Cortes
    The Lancet Oncology 08/2013; · 25.12 Impact Factor
  • Jose Perez-Garcia, Eva Muñoz-Couselo, Javier Cortes
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    ABSTRACT: Although the outcome of small (T1a/b) node-negative breast tumors is generally excellent, in the absence of prospective clinical trials, we are limited to data derived from retrospective analyses. Overall, the 10-year overall mortality rate is approximately 20%, while the 10-year breast cancer-specific mortality is in the range of 4% to 8% among this population in the absence of systemic therapy. This clearly reflects that many patients die of causes not related to breast cancer. Due in large part to breast cancer screening programs, the incidence of small tumors is increasing. There is consequently a growing interest in identifying factors that negatively affect the prognosis of these patients. Several studies have shown that patients with triple-negative and HER2+ tumors have a worse prognosis compared with hormone-receptor-positive, HER2- small breast cancers. However, the recent explosion of knowledge of the molecular characteristics of tumors is opening a new way to address cancer. Different genomic assays are currently available to help better predict the outcome of breast cancer patients. However, none of these techniques have been specifically evaluated in patients with small (T1a/b) node-negative tumors, and only a small number of patients with these tumors were included in those studies. In addition, very limited data are available about the role of these assays in patients with triple-negative or HER2-positive cancers. Although a chemotherapy-based strategy might be useful for triple-negative or HER2-positive T1b tumors, more information is urgently needed in order to optimize the treatment of our patients.
    American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting. 01/2013; 2013:25-31.
  • Jose Perez-Garcia, Javier Cortes
    The Lancet Oncology 08/2012; 13(9):850-1. · 25.12 Impact Factor
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    ABSTRACT: Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P < 0.001). Partial response was seen in 1 patient [1.2%, PI3K inhibitor with PIK3CA mutation] and stable disease >16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit. Mol Cancer Ther; 11(9); 2062-71. ©2012 AACR.
    Molecular Cancer Therapeutics 06/2012; 11(9):2062-71. · 5.60 Impact Factor
  • Expert Review of Anti-infective Therapy 06/2012; 12(6):703-5. · 3.06 Impact Factor
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    José Pérez-García, Javier Cortés
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    ABSTRACT: The current understanding of the molecular biology of breast cancer presents an extremely complex portrait of the disease. Based on this knowledge, considerable efforts are being made to identify biomarkers that will predict the response to a specific treatment while minimizing the risk of unnecessary side effects. In breast cancer, the Ki67 index has been associated with poor prognosis and might play a relevant role in predicting benefit from adjuvant docetaxel, as observed in the article accompanying this editorial. Taxanes are one of the most active cytotoxic agents for breast cancer. However, the role of taxane-based chemotherapy as adjuvant treatment of early breast cancer remains controversial in some subsets of patients. For this reason, the Ki67 index might help to better define the group of patients who could have the optimal benefit.
    Breast cancer research: BCR 01/2012; 14(1):104. · 5.87 Impact Factor
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    Eduardo Vilar, Jose Perez-Garcia, Josep Tabernero
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    ABSTRACT: The phosphatidylinositol-3-kinase (PI3K)/mTOR pathway has been a major focus of attention for cancer researchers in the past decade. A preliminary and incomplete understanding of the molecular biology of this complex network has importantly conditioned not only the development of the first generation of mTOR inhibitors, but also the biomarker studies designed to identify the best responders to these agents. Most recently, research in this pathway has focused on the dual nature of mTOR that is integrated by the mTOR complex 1 and complex 2. These two complexes are formed and regulated by different proteins and are also driven by multiple different compensatory feedback loops. This deeper understanding has allowed the development of a promising second generation of inhibitors, which are able to block simultaneously both complexes due to their catalytic activity over mTOR. Moreover, some of them also exert an inhibitory effect over PI3K that is a key player in the feedback loops. This article reviews the newest insights in the signaling of the mTOR pathway and then focuses on the development of the new wave of mTOR inhibitors.
    Molecular Cancer Therapeutics 01/2011; 10(3):395-403. · 5.60 Impact Factor
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    Eva Muñoz-Couselo, José Pérez-García, Javier Cortés
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    ABSTRACT: Metastatic breast cancer (MBC) remains an incurable disease, with the goals of care aimed at maximizing the patient's duration and quality of life. Treatment options for MBC have become more efficacious and numerous. In addition to endocrine and chemotherapy agents, a number of targeted agents, including trastuzumab and bevacizumab, have further enhanced the landscape of therapeutic options. Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor, and a structurally simplified synthetic analog of the natural marine product, halichondrin B, with a novel mechanism of action that has shown antitumor activity in pretreated MBC. Eribulin has shown a manageable tolerability profile in Phase I-II clinical trials and an improvement in overall survival compared with treatment of physician's choice, without relevant toxicities in a recently published Phase III trial. This review will focus on eribulin as a new active agent for MBC and its role in the management of breast disease.
    OncoTargets and Therapy 01/2011; 4:185-92. · 2.07 Impact Factor
  • European Journal of Cancer - EUR J CANCER. 01/2011; 47.
  • Annals of Oncology 04/2010; 21(4):907. · 7.38 Impact Factor
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    ABSTRACT: Differentiated thyroid carcinoma is the most frequent neoplasm of the endocrine system. Although thyroid cancer usually has an excellent prognosis, no therapeutic options are available for patients that develop metastases and are or became resistant to radioiodine therapy. The deeper knowledge of molecular aberrations that characterize tumor growth has provided novel targets in cancer therapy. Several proteins have been implicated as having a crucial role in the carcinogenesis of differentiated thyroid cancer, such as those involved in RET/PTC-RAS-RAF-MAPK pathway. Moreover, vascular aberrations and angiogenesis equilibrium have also been related to tumor growth. The development of new, targeted therapies and their encouraging initial results have opened a hopeful opportunity of treatment for these orphan therapy tumor patients.
    Targeted Oncology 11/2009; 4(4):275-85. · 3.46 Impact Factor
  • B Markman, F Atzori, J Pérez-García, J Tabernero, J Baselga
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    ABSTRACT: The phosphatidylinositol 3-kinase (PI3K) signalling pathway is integral to diverse cellular functions, including cellular proliferation, differentiation and survival. The 'phosphate and tensin homologue deleted from chromosome 10' (PTEN) tumor suppressor gene plays a critical role as a negative regulator of this pathway. An array of genetic mutations and amplifications has been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to some classic cytotoxics and targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex machinations and interactions. This knowledge has enabled the evolution of rationally designed drugs targeting elements of this pathway. It is important that the development of suitable biomarkers continues in parallel to optimize use of these agents. A new generation of PI3K inhibitors is now entering early clinical trials, with much anticipation that they will add to the growing armamentarium of targeted cancer therapeutics.
    Annals of Oncology 09/2009; 21(4):683-91. · 7.38 Impact Factor
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    European journal of cancer (Oxford, England: 1990) 09/2009; 45 Suppl 1:79-88. · 4.12 Impact Factor
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    ABSTRACT: In the last years, interesting advances have been reported in the treatment of infrequent digestive tumors. The increasing development of new targeted therapies in human cancer has also impacted in these rare gastrointestinal malignancies providing a wide range of possibilities in the design of future clinical trials. The inhibition of angiogenesis and the blockage of the epidermal growth factor receptor pathway have provided the most interesting activity in recently reported studies for esophageal and biliary tract carcinomas. Additionally, several targeted therapies have been developed to target the main kinase proteins of the most important pathways of these malignancies. The results of the biggest phase III trial in locally advanced anal carcinoma have been recently published. Finally, the inhibition of epidermal growth factor receptor has also showed promising activity in anal carcinomas. Recent advances in the knowledge of molecular mechanism of carcinogenesis have led to meaningful changes in the management of gastrointestinal cancers. Although the major advances in targeted therapy have been introduced in the treatment of colorectal cancer, new interesting approaches have been reported in less frequent gastrointestinal tumors such as esophageal, biliary tract, and anal canal carcinoma opening a new hope in the treatment of these rare tumors in the molecular targeted therapy era.
    Current opinion in oncology 05/2009; 21(4):374-80. · 4.09 Impact Factor
  • Therapy 01/2009; 6(3):321-333.

Publication Stats

115 Citations
266.75 Total Impact Points

Institutions

  • 2012–2014
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 2009–2014
    • University Hospital Vall d'Hebron
      • Department of Medical Oncology
      Barcino, Catalonia, Spain
  • 2009–2013
    • Vall d’Hebron Institute of Oncology
      Barcino, Catalonia, Spain
  • 2011
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, United States