Towards Personalized Cancer Medicine

Agenda

THURSDAY, MAY 20, 2010

Speaker abstracts are listed in order of presentation. A gap in the sequence of abstracts, indicates that an abstract was not received at the time of this posting.

Session III: Oncogenomics and Tumor Profiling

Signatures for Small Molecule Discovery

Todd R. Golub, MD, The Broad Institute of Harvard and MIT, Dana-Farber Cancer Institute, Boston, MA

The application of genomic approaches to the study of cancer holds tremendous promise for improved diagnostic and prognostic tests, and for the elucidation of new therapeutic targets by building a molecular taxonomy of the disease. More recently, we have addressed the challenge of using gene expression data in the drug discovery setting. That is, having defined a gene expression signature of a biological state of interest (e.g. tumor subtype or state of pathway activation), could a small molecule library be screened to identify compounds capable of modulating the signature of interest – and by inference, modulate the biological state under study. We piloted this idea, termed Gene Expresion-based High Throughput Screening (GE-HTS), and applied it to the discovery of compounds capable of inducing the myeloid differentiation of acute myeloid leukemia cells. Importantly, the discovery of these compounds did not require a specialized phenotypic assay, nor did it require prior knowledge of the mechanism by which differentiation occurs. We have subsequently applied this GE-HTS concept to the discovery of compounds that inhibit the activity of the Ewing Sarcoma oncogene EWS/FLI and that abrogate androgen receptor signaling in prostate cancer. These experiments establish the feasibility of using a gene expression signature as the read-out of a primary small-molecule screen. Extending on this concept of signature-based chemical screening, we have recently established the feasibility of using a database of gene expression profiles to systematically connect signatures of diseases to signatures of gene product function or signatures of drug action. We refer to this project as the Connectivity Map project. By querying a centrally generated database of gene expression profiles, users can find ‘connectivity’ between a query signature of interest and one or more treatments (perturbagens) in the database. The data and tools are available at www.broadinstitute.org/cmap and we have used the method to discover relevant connections in dexamethasone-resistant childhood leukemia, androgen response in prostate cancer, among many others. These experiments demonstrate the feasibility of the Connectivity Map approach, and suggest the value of creating a larger, more extensive, publicly accessible Connectivity Map database. Toward that goal, we have piloted a low-cost, high throughput approach based on a reduced representation of the transcriptome capable of supporting truly genome-scale data generation.

Gene Fusion Discovery in Cancer

Arul M. Chinnaiyan, MD, PhD, S.P. Hicks Endowed Professor of Pathology, American Cancer Society Research Professor, University of Michigan Medical School

To date, the great majority of disease-specific, recurrent chromosomal rearrangements have been characterized in hematological malignancies and mesenchymal tumors and not in common epithelial tumors such as breast, lung, colon, or prostate cancer. Here, we employed a bioinformatics approach on a compendium of cancer gene expression data to discover candidate oncogenic chromosomal aberrations based on outlier gene expression. In addition to identifying many gene partners of characteristic rearrangements in human malignancies, this approach identified two members of the ETS family of transcription factors, ERG and ETV1, as outliers in prostate cancer. Either ERG or ETV1 was over-expressed in the majority of prostate cancers (50-70%) and were mutually exclusive across several independent gene expression datasets, suggesting that they may be functionally redundant in prostate cancer development.

By RNA ligase-mediated rapid amplification of cDNA ends (RACE), we identified a recurring gene fusion of the 5’ untranslated region of a prostate-specific, androgen-regulated gene TMPRSS2 to ERG or ETV1 in prostate cancer cases which over-expressed the respective ETS family member. These gene fusions were confirmed using quantitative PCR (QPCR) and sequencing of reverse transcription PCR products. In addition, using fluorescence in situ hybridization (FISH), we demonstrated that 23 of 29 (79%) prostate cancer samples harbor rearrangements in ERG or ETV1. Furthermore, in vitro cell line studies suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the aberrant over-expression of ETS family members in prostate cancer. Subsequently, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified outlier expression of ETV4 in two of 98 cases. In one such case, we confirmed the over-expression of ETV4, and by RACE, QPCR and FISH, we identified fusion of the TMPRSS2 and ETV4 loci.

Together, these results suggest a pathogenetically important role for recurrent chromosomal rearrangements in common epithelial tumors and have implications in the molecular diagnosis and treatment of prostate cancer. Importantly, these results identify three molecular subtypes of prostate cancer, TMPRSS2:ERG, TMPRSS2:ETV1 and TMPRSS2:ETV4, and suggest that dysregulation of ETS family member expression through gene fusions with TMPRSS2 may be a generalized mechanism for prostate cancer development.

In our most recent work, we explored the mechanism of ETS family over-expression in prostate tumors. Remarkably, we identified novel 5’ fusion partners in prostate tumors with outlier expression of ETS family members, including untranslated regions from a prostate-specific androgen-induced gene and endogenous retroviral element, a prostate-specific androgen-repressed gene, and a strongly expressed housekeeping gene. As the commonality of these rearrangements is the aberrant over-expression of ETS genes, we recapitulated this event in vitro. We demonstrate that ETS over-expression in multiple benign prostate cells induces a marked increase in invasion, confirming the role of ETS gene rearrangements in prostate cancer development. Identification of distinct classes of ETS gene rearrangements demonstrates that dormant oncogenes can be activated in prostate cancer by juxtaposition to tissue-specific or ubiquitously active genomic loci. Subversion of active genomic regulatory elements may serve as a more generalized mechanism for carcinoma development. Furthermore, the identification of androgen-repressed and insensitive 5’ fusion partners has important implications for the anti-androgen treatment of advanced prostate cancer.

The Role of BNIP3 in Cell Proliferation and Hypoxia-Induced Autophagy: Implications for Personalized Cancer Therapies

Meghan B. Azad, BSc,1-3 and Spencer B. Gibson.1-3 1Manitoba Institute of Cell Biology, 2CancerCare Manitoba, 3Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

Autophagy is a regulated lysosomal degradation pathway that functions in both cell survival and cell death. The role of autophagy in cancer progression and treatment is controversial, since it may be protective or destructive to tumor cells depending on individual genetic signatures and treatment conditions. Hypoxia (low oxygen) is often associated with solid tumors, correlating with poor prognosis because hypoxia confers resistance to radiation and chemotherapy. Using multiple cancer cell lines, we have shown that chronic hypoxia can induce autophagic cell death through a mechanism involving BNIP3, a hypoxia-inducible pro-death Bcl-2 family member that is frequently altered in tumors. BNIP3 itself induces autophagic cell death, and BNIP3 knock-down protects against hypoxia-induced autophagy and cell death. Using a BNIP3-/- mouse model, we have additionally determined that loss of BNIP3 provides a growth advantage both in vivo and in vitro. Ongoing studies include protein expression analysis in various tissues and characterization of proliferation, autophagy and cell death in cultured primary astrocytes and embryonic fibroblasts.

Given the potential for personalized cancer therapy based on individual tumor characteristics (including autophagic capacity, hypoxic status, and BNIP3 activity), we ultimately intend to study hypoxia-induced autophagy in tumor development, progression and treatment using the BNIP3-/- mouse model.

Transcriptional Profiling Analysis Reveals a 7-Gene Signature Diagnostic of Prostate Cancer and a Recurrent Gain on 17q25.3

R. Bermudo, PhD,1,2, D. Abia3, B. Ferrer4, I. Nayach4, A. Benguria5, Á. Zaballos5, J. del Rey6, R. Miró6, E. Campo4, C. Martínez-Alonso5, Á. R. Ortiz3, P. L. Fernández1,4 and T. M. Thomson2 1Institut d’Investigacions Biomèdiques August Pi i Sunyer, Barcelona, 2Institut de Biologia Molecular de Barcelona, Barcelona, 3Centro de Biología Molecular Severo Ochoa, Madrid, 4Hospital Clínic de Barcelona, Barcelona, 5Centro Nacional de Biotecnología, Madrid, 6Universitat Autònoma de Barcelona, Barcelona

Transcriptional profiling of prostate cancer (PC) has permitted us to identify signatures corresponding to non-tumoral luminal and tumoral epithelium, basal epithelial cells, and prostate stromal tissue. After real-time RT-PCR validation and Linear Discriminant Analysis, we identified a 7-gene signature whose combined profiles allowed robust discrimination between normal and tumor prostate samples in 100 % of cases, including samples distinct from those used in the original microarray analysis and external datasets. Individual genes in this signature (ABCC4, MYO6 and EphA2) were also validated by immunohistochemistry on archival samples. Additional analysis identified sets of co-expressed transcripts whose genes co-localize in the genome, in particular associated with 17q25.3. This computational inference was validated by FISH, which demonstrated gains in this region in over 60% of prostate cancer samples.

Additionally, when PIN lesions could be analyzed near tumoral zones with the gain, we also found this chromosomic alteration, suggesting that it is an early event in PC. Finally, the frequent finding of this gain in more than 60% of metastatic samples indicates that this alteration is conserved during all steps of tumor progression.

Finding Mechanisms and Biomarkers of Drug Resistance in Cancer

René Bernards, PhD, Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam

Unresponsiveness to therapy remains a significant problem in the treatment of cancer, also with the new classes of targeted therapeutics. In my laboratory, we use functional genetic approaches to identify biomarkers that can predict responsiveness to clinically relevant cancer therapeutics. We focus on targeted cancer drugs such as trastuzumab (Herceptin), PI3K inhibitors, MEK inhibitors, ALK inhibitors, mTOR inhibitors, Histone Deacetylase inhibitors and retinoic acid. These drug target specific molecules or pathways that are often activated in cancer. Nevertheless, it remains poorly explained why a significant number of tumors do not respond to the therapy. We aim to elucidate the molecular pathways that contribute to unresponsiveness to targeted cancer therapeutics using a functional genetic approach. This will yield biomarkers that may be useful to predict how individual patients will respond to these drugs. Furthermore, this work may allow the development of drugs that act in synergy with the established drug in the treatment of cancer.

To identify biomarkers that control tumor cell responsiveness to cancer therapeutics, we use two complementary approaches. First, we use genome wide loss-of-function genetic screens (with shRNA interference libraries) in cancer cells that are sensitive to the drug-of-interest to search for genes whose down-regulation confers resistance to the drug-of-interest (resistance screens). In addition, we use single well siRNA screens with a low dose of the drug to screen for genes whose inhibition enhances the toxicity of the cancer drug (sensitizer screens). Once we have identified resistance and/or sensitizer genes, we ask if their expression is correlated with clinical response to the drug-of-interest using tumor samples of cancer patients treated with the drug in question, whose response to therapy is documented. Examples of genetic screens to identify mechanisms of resistance to different cancer drugs will be presented.

Causes and Consequences of microRNA Dysregulation in Cancer

Carlo M. Croce, MD, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center

During the past several years it has become clear that alterations in the expression of microRNA genes contribute to the pathogenesis of most, perhaps all, human malignancies. These alterations can be caused by a variety of mechanisms, including deletions, amplifications or mutations involving microRNA loci, by epigenetic silencing or by dysregulation of transcription factors targeting specific microRNAs. Since malignant cells show dependence on the dysregulated expression of microRNA genes, which in turn control or are controlled by dysregulation of multiple protein coding oncogenes or tumor suppressor genes, these small RNAs provide important opportunities for development of future microRNA based therapies.

Translating the Cancer Genomes

Lynda Chin, MD, Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute, Boston, MA

Cancer cells are endowed with diverse biological capabilities driven by myriad inherited and somatic genetic and epigenetic aberrations that commandeer key cancer-relevant pathways. Our increasing ability to comprehensively characterize the landscape of the cancer genomes in a large number of clinically annotated tumor specimens holds enormous potential to (i) provide penetrating and definitive insight into the genetic bases of cancer, (ii) identify promising candidate therapeutic targets and diagnostic biomarkers, and (iii) illuminate the path toward personalized cancer medicine. The challenge beyond data generation is “making sense” of the cancer genomes to understand how the ensemble of these aberrations collaborates to drive cancer pathophysiology. Approaches to translate these complex cancer genomic information into biological insights will be discussed, including cross-species comparative oncogenomics, functional genetic screens and deep biology studies.

Session IV: Biomarkers for Prognosis/Response: Impact on Clinical Trials

Molecular Portraits of Breast Tumors

Charles M. Perou, PhD, Departments of Genetics and Pathology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC

Breast cancer is a heterogeneous disease in terms of histology, dissemination patterns, therapeutic responses, and patient outcomes. Gene expression analyses using DNA microarrays have helped to explain some of this heterogeneity and provided important new clues as to the cellular origins of many breast tumors. Our studies using gene expression profiling have established five major breast cancer intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, Claudin-low, Basal-like) and a Normal Breast-like group, with these tumor subtypes showing significant differences in patient survival and in frequencies according to race and stage. Mounting evidence also suggests that these subtypes vary in their responsiveness to chemotherapeutics and biologic agents. In fact, the expression of drug targets like ER, PR, HER1, and HER2 within only certain subtypes, suggests that more individualized therapeutic approaches could be based upon a patients tumor subtype. therefore, I will present the available data concerning the responsiveness of the intrinsic subtypes relative to chemotherapeutics and tamoxifen therapy and show that this classification provides predictive information.

Recently, FACS analysis of normal human mammary epithelial cells, mouse tumors, and human cell lines, have identified a mammary luminal cell developmental pathway starting from a bi-potent stem cell, to a luminal progenitor, and ending in a mature ER+ luminal cell. We compared the genomic profiles of each intrinsic subtype to that of the profiles coming from FACS isolated human mammary epithelial cell populations and determined that the Claudin-low subtype was the most similar to the normal mammary epithelial stem cell. This unique subtype also shows many mesenchymal features including high expression of SNAIL and VIMENTIN. We postulate that the observed intrinsic subtypes of breast cancer mimic normal mammary development with each subtype representing a distinct stage of epithelial cell development. These findings also have important implications for the potential cell type of transformation of each subtype, which may be a stem cell for some subtypes (Claudin-low and Basal-like) and a differentiated cell for others (Luminal A).

Predictive Biomarkers in Management of EGFR Mutant Lung Cancer

Rafael Rosell, MD, Miquel Taron, Teresa Moran, Miguel Angel Molina, Carlota Costa, Susana Benlloch, Bartomeu Massuti, Catalan Institute of Oncology; Pangaea Biotech, USP Instituto Universitario Dexeus, Barcelona

Non-small-cell lung cancer (NSCLC) driven by EGFR mutations occurs predominantly in never-smokers, women and non-squamous cell histologies. In the European population, the overall frequency of EGFR mutations is 15-17%; however, this can reach 40% in never-smokers, compared to 10% in former smokers and 5% in current smokers. In females, the probability of finding mutations is 30%, compared to 10% in males. The predominant histological subtype of adenocarcinoma could have some influence on the frequency of EGFR mutations although more clinical data is needed. A large prospective study in patients with EGFR mutations showed that response to erlotinib was 70%, progression free survival was 14 months, and median survival was 27 months. Acquired resistance has been related to the presence of the EGFR T790M mutation, and specific inhibitors of the T790M mutation are promising. Additionally, the overexpression of MET has been reported to be relevant. The detection of T790M is a technical issue that can be solved with an adequate laboratory assay. We have detected EGFR double mutations (T790M plus deletions or L858R) in 35% of pretreatment biopsies from 129 NSCLC patients and observed a negative correlation with progression free survival to erlotinib. The baseline gene expression of other receptor tyrosine kinases, such as MET, AXL, IGF-1R and IL-6 did not influence erlotinib outcomes.

Erlotinib can cause double-strand breaks that are repaired mainly by homologous recombination. In experimental models, erlotinib sensitivity is highly influenced by BRCA1 status. In our experience, low levels of BRCA1 mRNA can prolong progression free survival to 27 months. In the multivariate analysis of progression free survival, only T790M, BRCA1 and PP2A/C were independent prognostic markers. In the multivariate analysis of survival, only T790M and BRCA1 were identified as independent markers.

Based on our findings, we do not believe that T790M is the main cause of acquired resistance. Rather, we speculate that the amplification of the pathway of H2AX/RNF8/RNF168/RAP80/ BRCA1 could be a main cause of resistance to protracted treatment with erlotinib. At present, we are investigating the role of BRCA1 SUMOylation and sensitivity to erlotinib.

A Precise EGFR Signal Output Determines the Response of Cells Expressing Glioblastoma-Associated Ectodomain Mutant EGFR to a Small Molecule Tyrosine Kinase Inhibitor, Regardless of PTEN Status

Igor Vivanco, PhD1, Daniel Rohle1,2, Carl Campos1, Nicolas Yannuzzi1, and Ingo Mellinghoff1,2,3. 1Human Oncology and Pathogenesis Program and 3Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, New York; 2Department of Pharmacology, Cornell University, New York, New York

Missense mutations in the extracellular (EC) domain of EGFR have been identified in a subgroup of glioblastomas, and have been shown to be oncogenic in experimental models. However, the continued requirement for mutant EGFR function for tumor maintenance has yet to be demonstrated. Using a number of cell lines that naturally express EC mutant EGFR and through pharmacological and RNAi approaches, we have uncovered a dependence on EGFR in the survival of these cells. Interestingly, we find that cell death only occurs when near complete inhibition of EGFR has been reached, and only after complete proliferation arrest has been achieved. Furthermore, this level of target inhibition was drug-specific. The sum of these results is consistent with the existence of a precise EGFR activity threshold responsible for maintaining survival in these cells. A comparison of various treatment regimens in a xenograft model confirmed that only drug doses high enough to fully block EGFR activation exhibit anti-tumor activity. Finally, we found that unlike the effect of PTEN on EGFR inhibitor responses in cells with other EGFR genotypes, the response to EGFR tyrosine kinase inhibitor in EC-mutant-EGFR-expressing cells is unaffected by PTEN inactivation. Our findings strongly suggest that meaningful clinical responses to EGFR inhibitors will likely depend on several factors including potency of inhibition and target genotype.

A Major Role of 611-CTF, a Carboxy-Terminal Fragment of HER2, in the Downmodulation of ER in HER2-Positive Breast Cancers

Josep Lluís Parra-Palau, Kim Pedersen, Vicente Peg, Maurizio Scaltriti, Pier Davide Angelini, Marta Escorihuela, Sandra Mancilla, Alexandre Sánchez Pla, Santiago Ramón y Cajal, José Baselga & Joaquín Arribas, PhD, Vall d’Hebron Institute of Oncology, Barcelona

Current classification of breast cancers depends in great part on the expression of HER2, a cell surface tyrosine kinase receptor, and ER, the nuclear receptor for estrogen. In addition to reliable biomarkers, these receptors are targets of effective and widely used anti-tumor drugs. However, during malignant progression HER2 and ER can establish an intricate cross-talk. HER2 overexpression may lead to the downregulation of ER and undermining of anti-ER therapies. A subgroup of HER2-positive breast cancer patients of bad prognosis expresses a heterogeneous series of HER2 carboxy-terminal fragments (CTFs) collectively known as p95HER2. One of these fragments, 611-CTF, is oncogenic in a variety of preclinical models. Because of the lack of an appropriate tool to specifically analyze its levels in the clinical setting, the value of 611-CTF as a biomarker has not been established yet. Here we show that 611-CTF induces a more pronounced downmodulation of ER than that induced by full-length HER2. To validate this effect in breast cancer samples, we developed specific anti-611-CTF antibodies. With these antibodies, we showed that while the frequency of ER positivity in HER2-positive/CTF-611-negative samples (72.6%) is similar to that reported for HER2-negative patients (70-80 %), the number of ER-positive patients in the 611-CTF-positive subgroup is very low (31.2%). These results confirm that 611-CTF plays a major role in the regulation of ER and suggest that the expression of this HER2 isoform diminishes the responsiveness to endocrine therapy.

Guiding Cancer Treatment through Personalized TumorgraftTM Models

Manuel Hidalgo, MD, PhD1,2, Steve Strawn, B.S., M.A.2, N.V. Rajeshkumar, Ph.D.1, I Garrido-Laguna1, David Sidransky, M.D.1 and Elizabeth Bruckheimer Ph.D.2 1Johns Hopkins University, 2Champions Biotechnology, Inc. Baltimore, MD

One of the key challenges facing oncology drug development is the high attrition rates of compounds that enter the drug development pipeline. Champions Biotechnology, has developed a novel preclinical platform derived from Personalized Biomerk Tumorgraft™ models; an innovative approach that utilizes the implantation of the patient’s own tumors in immune-deficient mice in a manner that preserves the biological properties of the original human tumor. In the current study, Personalized Tumorgraft™ models were generated from 10 patients diagnosed with advanced, standard of care refractory cancers. Tumor fragments were implanted in nude mice and propagated as tumor fragments to generate homogeneously growing tumors suitable for drug treatments. From this, the most effective treatment was selected for application to clinical care. Overall, 16 Tumorgraft recommended treatments have been administered to 10 patients which resulted in a 100 % correlation of both positive and negative predictive values. Of the 8 patients treated with a Tumorgraft recommended drug regimen, all achieved long-lasting partial/complete responses including two patients with 36+ months survival. Additionally, biological studies in these Tumorgraft models provided a unique opportunity to discover new biomarkers. In summary, we demonstrate that generation of Personalized Tumorgrafts that can be used for extensive personalized drug screening studies leading to the selection of clinically effective agents. Moreover, the correlation between Tumorgraft response in mice and clinical activity in the patients administered the Tumorgraft recommended treatments demonstrates the predictive nature of the Personalized Tumorgraft models and supports this platform in oncology drug development through the discovery new biomarkers and the understanding of a drug´s mechanism of action.

Breast Cancer Biomarkers to Guide Treatment Decisions

Laura J. van ‘t Veer, PhD, Cancer Center University of California San Francisco, US; The Netherlands Cancer Institute, Amsterdam, The Netherlands

The conventional approach to cancer therapy, to treat according to the organ or tissue of origin and patients’ demographics, is gradually being replaced by a more personalized approach in which treatment choice is based on detailed knowledge of the genetic defects that underlie the oncogenic process in each individual tumor. As a result, we have witnessed the beginning of a shift from broadly-acting cytotoxic drugs towards more specific and less toxic targeted therapies. At the same time, the annotation of the human genome has enabled the development of a new class of gene expression-based molecular diagnostics that help identify those patients, which require therapy and those, which are most likely to benefit from such targeted therapies. Such molecular diagnostics increasingly impacts patient management.

Integrated Analysis of Lung Cancer Reveals Molecular Architecture and Suggests Selection Criteria for Treatment with Targeted Therapies

Andrey Loboda1, Carolyn Buser-Doepner1, Razvan Cristescu1, Michael Nebozhyn1, Theresa Zhang1, Pearl Huang2, James Watters, PhD1; Departments of 1Molecular Profiling and Research Informatics and 2Oncology, Merck & Co., Inc., North Wales, PA, USA

While multiple targeted therapies are currently undergoing clinical development, knowledge of the molecular determinants of response to these inhibitors continues to emerge. We will describe an approach that combines integrated analysis of human disease biology with preclinical models of efficacy, resulting in a molecular portrait that enables the identification of candidate responder populations in lung cancer. We will present an integrated, genome-wide analysis of mRNA, DNA copy number, and somatic mutation profiles across approximately human 500 lung cancers and 100 lung cancer cell lines. This analysis reveals molecular subtypes, deregulated pathways within subtypes, likely drivers of deregulated pathways, and the prevalence of these biomarkers across lung cancers. By combining these results with drug response data from pre-clinical model systems, a molecular classification scheme emerges that can be used to guide the development of targeted therapeutics. This systems-level view will contribute to the understanding and personalized treatment of lung cancer.

Travel & Lodging

Location

Isaac Newton, 26
Barcelona, Spain
Tel. 93 212 60 50 • Fax: 93 253 74 73

Public Transportation

Bus
17, 22, 58, 73, 75, 60 y 196

Tramvia Blau

Train: Ferrocarriles de la Generalitat
Avinguda del Tibidabo Station, followed by a short walk or bus 196

Driving
Exits Ronda de Dalt 6 y 7

Shuttle Buses to and from the Conference Center (CosmoCaixa)

During the conference, shuttle bus transportation will be available for participants with hotel reservations in downtown Barcelona. Shuttle buses will depart in the morning from the Jazz Hotel in downtown Barcelona (C/Pelai 3 – see below) and return to this hotel at the end of the day (schedule follows). There are no hotels within walking distance of CosmoCaixa, and thus we recommend that participants book a hotel in downtown Barcelona around Plaza Catalunya, which is in close proximity to the Jazz Hotel and public transportation (Ferrocalines de Cataluña or bus # 17).

Bus Schedule
Passengers are advised to report 10 minutes prior to scheduled departure.

Wednesday, May 19 - From Jazz Hotel
06:30 AM

Wednesday, May 19 - From CosmoCaixa
18:15 PM

Thursday, May 20 - From Jazz Hotel
06:45 AM

Thursday, May 20 - From CosmoCaixa
20:15 PM

Friday, May 21 - From Jazz Hotel
06:45 AM

Friday, May 21 - From CosmoCaixa
17:45 PM

Suggested Hotel Accommodations in Downtown Barcelona (within walking distance of the Jazz Hotel and public transportation)

Hotel Jazz
Address: C Pelai, 3, bxs
Telephone: 935529696 / Fax: 935529697
Web: http://www.nnhotels.es/
E-mail: jazz@nnhotels.es

Hotel Catalonia Ramblas
Address: C Pelai, 28
Telephone: 933168400 / Fax: 933168401
Web: http://www.hoteles-catalonia.es
E-mail: ramblas@hoteles-catalonia.es

Hotel H10 Universitat
Address: Rda Universitat 21
Telephone: 933427850 / Fax: 933024907
Web: http://www.h10.es
E-mail: h10.universitat@h10.es

Hotel Regina
Address: C Bergara, 2*4
Telephone: 933013232 / Fax: 933182326
Web: http://www.reginahotel.com
E-mail: reservas@reginahotel.com

Hotel Catalonia Duques de Bergara
Address: Bergara, 11
Telephone: 933015151 / Fax: 933173442
Web: http://www.hoteles-catalonia.es
E-mail: duques@hoteles-catalonia.es

Hotel Pulitzer
Address: C Bergara, 8
Telephone: 934816767
Web: http://www.hotelpulitzer.es
E-mail: info@hotelpulitzer.es

Hotel Soho
Gran Vía, 543-545
Telephone: 93 552 96 10 / Fax: 93 552 96 11
Web:http://www.hotelsohobarcelona.com/
EMAIL: soho@nnhotels.com

Hotel Reding
Address: Gravina, 5*7
Telephone: 934121097 / Fax: 932683482
Web: http://www.hotelreding.com
E-mail: reding@occidental-hoteles.com

Hotel H10 Gravina
Address: Gravina, 12
Telephone: 933016868 / Fax: 933172838
Web: http://www.h10.es
E-mail: h10.gravina@h10.es

Hotel Inglaterra
Address: Pelai, 14
Telephone: 934873939 / Fax: 935051109
Web: http://www.hotel-inglaterra.com
E-mail: recepcion@hotel-inglaterra.com

Hotel Ciutat Vella
Address: C Tallers, 66
Telephone: 934813799 / Fax: 934813805
Web: http://www.hotelciutatvella.com
E-mail: info@hotelciutatvella.com

Hotel Atlantis
Address: C Pelai, 20
Telephone: 933189012 / Fax: 934120914
Web: http://www.hotelatlantis-bcn.com
E-mail: info@hotelatlantis-bcn.com

Hotel Lleó
Address: C Pelai, 22
Telephone: 933181039 / Fax: 934122657
Web: http://www.hotel-lleo.es
E-mail: reservas@hotel-lleo.es

For more information about these and other hotels around Plaza de Catalunya and La Rambla, click here.

If you wish to explore other options click here (select district: Eixample or Ciutat Vella).

General Information about Barcelona

Please visit the website linked here.

Special Needs and Additional Information

For any additional information and for special needs, please e-mail Renee Wilkerson at rwilkerson@nyas.org or call 212.298.8618.