Download programa - La Fundación Lilly

-PROGRAMA-
Chairmen / Directores: Miguel A Piris and Manuel Morente
Lugar / Place: EUROFORUM INFANTES, San Lorenzo de El Escorial, Madrid
Fecha / Date: March 26th & 27th, 2009
JUEVES/ Thursday, March / 26th
08:00
08:20
SESIÓN 1
08:40
Recogida de Acreditaciones / Registration
Bienvenida y apertura / Welcome & Opening
CANCER GENOMICS I / GENÓMICA DEL CÁNCER I
Chairperson / Moderador: Mariano Barbacid, CNIO, Madrid, Spain
Tom Hudson, Ontario Institute for Cancer Research, Ontario, Canada
The International Cancer Genome Consortium / Consorcio Internacional del
Genoma del Cáncer
(+ info)
09:20
The International Cancer Genome Consortium (ICGC) was launched in April 2008 to
coordinate an international-scale research effort to understand the genomic,
transcriptomic and epigenetic changes involved in the major forms of cancer. The ICGC
will produce comprehensive catalogues of the full range of genetic mutations involved
in the world’s major types of cancer, with key factors being the ability to detect all
mutated cancer genes, data at the level of individual DNA bases, application of
common standards for pathology and technology and comparison data from matched,
non-tumor tissue. This information will lead to better ways of diagnosing, treating and
preventing cancer.
Victor E Velculescu, Johns Hopkins, Baltimore, MD, USA
The genomic landscapes of human cancer / Panorámicas genómicas del
cáncer humano
(+ info)
10:10
It is generally accepted that cancer is a disease caused by accumulation of mutations
in specific genes. These tumor-specific mutations provide clues to the cellular
processes underlying tumorigenesis and have proven useful for diagnostic and
therapeutic purposes. To date, however, only a small fraction of the genes has been
analyzed and the number and type of alterations responsible for the development of
common tumor types are unknown. We have recently begun a systematic study of the
cancer genome through analysis of the majority of protein coding genes in breast,
colorectal, pancreatic and brain cancers. These analyses have identified a wealth of
new genes and pathways that had not been previously linked to human cancer. Our
studies define the genetic landscape of human cancers, provide new targets for
personalized intervention, and open fertile avenues for basic research in tumor biology.
Rene Bernards, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Finding biomarkers of drug resistance using functional genetic approaches /
Identificación de biomarcadores de resistencia farmacológica mediante
genómica funcional
Targeted cancer therapies, like conventional cancer therapies, also suffer from the
development of resistance. In my laboratory, we use large-scale loss of function
genetic screens to find genes whose suppression causes resistance to targeted cancer
drugs. Such genes are of interest because they are modulators of the pathway that is
targeted by the drug, but also because these genes are potential biomarkers to predict
responses to these drugs in the clinic.
(+ info)
10:40
Café / Coffee
SESIÓN 2
11:10
CANCER GENOMICS II / GENÓMICA DEL CÁNCER II
Chairperson / Moderador: Miguel A Piris, CNIO, Madrid, Spain
Miguel A Piris, CNIO, Madrid, Spain
Targets in B-cell lymphoma / Dianas en los linfomas de células B
Lymphoid neoplasms are a heterogeneous group of lymphoproliferative malignancies
with differing patterns of behaviour and responses to treatment. Standard
treatments (cytotoxic therapy and immunotherapy) fail to cure roughly half of the
patients, leading also to side effects with significant morbidity. Data generated by
high-throughput and functional studies are showing that B-cell receptor (BCR)
provides the neoplastic B-cells with essential survival signalling. Our effort is
currently aimed to target signalling pathways and genes coupled to BCR.
(+ info)
11:50
Todd R Golub, Harvard Medical School, Boston, MA, USA
Genomic signatures of cancer / Patrones genómicos del cáncer
Comprehensive views of the cancer genome are now becoming feasible and have
potential for significant impact on the development of cancer therapeutics. Data will be
presented that illustrate the ability to generate genome-wide data at the level of DNA,
mRNA (including profiling of routinely-collected formalin-fixed paraffin-embedded
tissues), and the phosphoproteome. Use of such data for the development of
diagnostic and prognostic biomarkers will be presented, as will the use of these
genomic signatures as a read-out for small molecule screens.
(+ info)
12:30
Matthew Meyerson, Harvard Medical School, Boston, MA, USA
Genomic alterations in human cancer / Alteraciones genómicas en el cáncer
humano
(+ info)
13:10
Cancer is a disease of the genome. High-throughput genome analysis tools now enable the
detection of somatic alterations in cancer cells including point mutations, copy number alterations,
translocations, and infections. To find copy number alterations, we have now analyzed over 2,600
cancer samples with arrays representing 250,000 mapped single nucleotide polymorphisms (SNPs),
or most recently, over 1.8 million mapped probe sets. Major discoveries include the identification of
lineage-specific amplification of the NKX2-1 gene in human lung adenocarcinoma (Weir et al.,
2007) Most recently, we have identified a counterpart amplified gene in squamous cell carcinomas.
To find mutations, we are performing systematic sequencing of selected gene families. Here, major
discoveries include activation mutations of the epidermal growth factor receptor tyrosine kinase
gene, EGFR, in human lung adenocarcinomas (Paez et al., 2004) and glioblastomas, the fibroblast
growth factor receptor 2 gene, FGFR2, in endometrial carcinomas (Dutt et al., 2008), and the
anaplastic lymphoma kinase, ALK, in neuroblastomas (George et al., 2008). EGFR, FGFR, and ALK
inhibitors respectively kill cells bearing these mutations. Furthermore, we have identified a total of
26 genes that are recurrently mutated in lung adenocarcinoma (Ding et al., 2008). To further
systematic genome discovery in well-annotated cancers, the National Institutes of Health have
established “The Cancer Genome Atlas” project. This consortium has now completed preliminary
analyses of 206 glioblastoma tumor DNA and RNA specimens and identified significant genomic
alterations including mutation of the PI3 kinase regulatory subunit gene, PIK3R1 (TCGA Network,
2008).
- Lilly Foundation Distinguished Career Award Ceremony POSTERS SESSION
13:40
SESIÓN 3
15:20
Almuerzo / Lunch
CANCER BIOMARKERS / BIOMARCADORES DE CÁNCER
Chairperson / Moderador: Ramón Colomer Bosch, M.D. Anderson, Madrid, Spain
Manuel Morente, CNIO, Madrid, Spain
Quality in tumor samples. A limiting step in cancer research / Calidad de las
muestras biológicas. Un factor limitante en investigación oncológica
(+ info)
Translational cancer research is highly dependent of series of cases including high quality
samples and their associated data. An easier access to these samples for the scientific
community is considered as the main bottleneck for research for health, and biobanks are
the most adequate site to try to resolve this issue. However, biobanks should not be
considered a static activity. On the contrary, biobanking is a young discipline which need
continuously evolve according to the permanent development of new techniques and new
scientific goals.
To accomplish current requirements of the scientific community biobanks need to face some
essential challenges including an appropriate design including networking, harmonized and
more suitable procedures, and sustainability, all of them in the framework of their ethic,
legal and social dimensions.
16:00
Rafael Rosell, Germans Trias i Pujol Hospital, Barcelona, Spain
Therapy response predictors in lung cancer / Predictores de respuesta terapéutica en
cáncer de pulmón
(+ info)
16:40
17:00
Aberrant signaling generated by the activation of multiple pathways occurs in cancers and
contributes to their growth, invasion and survival. Lung cancer-specific EGFR mutations
represent a new paradigm of genotyping. In 217 patients with multiple metastases, daily
erlotinib attained a 70% response rate, a 14-month time to progression, and a 27-month
median survival. Central to DNA damage response is the breast cancer gene 1 (BRCA1). The
predictive value of the BRCA1-RAP80-Abraxas complex was examined in metastatic lung
cancer patients. A sub-group of patients attained an unprecedented time to progression of 14
months and median survival not reached. Genotyping for appropriate targeted therapy and
customized chemotherapy can improve outcomes in several tumors.
Café / Coffee
Jose Costa, Yale University School of Medicine, New Haven, CT, USA
Tumor biomarkers in the century of Systems Biology / Biomarcadores tumorales en
el siglo de la Biología de Sistemas
Novel technologies and computational biology make it possible to begin to deconvolute the
complexity of cancer. The promise and challenges of systems biology for the field of
biomarkers will be discussed with an emphasis on new multiparametric tests and their use in
the cancer clinic.
(+ info)
17:40
Dan Theodorescu, University of Virginia Health Sciences Center, Charlottesville, VA, USA
COXEN-A way forward in personalized cancer therapy and drug discovery /
COXEN-A en terapia oncológica personalizada y descubrimiento de nuevas drogas
We demonstrate a novel, facile yet powerful approach to biomarker derivation that identifies
patients most likely to benefit from selected multi-agent therapy. Use of such tools, provides a
robust and generalizable approach to personalized cancer therapy with far reaching
applications in drug discovery, drug salvage and forecasting of novel single and combination
drug effectiveness in cancer patients.
(+ info)
VIERNES/ Friday, March /27th
SESIÓN 4
08:20
MOLECULAR TARGETS / DIANAS MOLECULARES
Chairperson / Moderador: Juan A Velasco, Lilly Research Labs, Madrid, Spain
Mariano Barbacid, CNIO, Madrid, Spain
Mouse tumor models and target validation / Modelos tumorales en ratones y
validación de dianas
(+ info)
To date, more than 500 genes have been found mutated in human cancer, thus providing a
wealth of therapeutic targets. Unfortunately, only a handful of these mutated genes encode
druggable products. Moreover, even in those the cases in which the mutated protein can be
pharmacologically inhibited (protein kinases, growth factors, receptors, etc.), the degree of
therapeutic efficacy observed has been rather modest, with the exception of Gleevec and
possibly Herceptin. A plausible explanation for these observations has been recently provided
by sequencing cancer genomes. Advanced tumors carry mutations in multiple pathways, thus
suggesting that successfully cancer therapies will require combinations of drugs capable of
blocking two or possibly more distinct pathways. In order to devise better strategies to block
oncogenic signaling, we have developed mouse tumor models that faithfully resemble those
observed in human patients. These mice can be endowed with conditional mutations whose
activation specifically ablates putative therapeutic targets. I will present our most recent
results following these basic strategies to evaluate the therapeutic effect of ablating the Raf,
Mek and Erk kinases as well as the cell cycle Cdks (Cdk2, Cdk4 and Cdk6) in K-Ras induced
NSCLCs.
09:00
Robert Kerbel, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Some mechanisms and consequences of antiangiogenic targeting of the VEGF
pathway in cancer / Algunos mecanismos y consecuencias de la actuación a través
de VEGF como diana de inhibición de angiogénesis en cáncer
Bedside to bench translational studies will be summarized with respect to a number of
important questions which have emerged from the clinical use and benefits of approved
antiangiogenic drugs. The research summarized is devoted to addressing some of the reasons
for the thus far transitory and modest benefits of antiangiogenic therapies for the treatment of
advanced metastatic disease. Some strategies for improving antiangiogenic therapies will be
outlined such as combination with other treatments, e.g. metronomic low-dose chemotherapy.
(+ info)
09:40
Kari Alitalo, Biomedicum Helsinki and the Haartman Institute, University of Helsinki, Finland
Targeting VEGF receptor pathways for inhibition of angiogenesis, lymphangiogenesis
and metastasis / El receptor de VEGF como diana de inhibición de angiogénesis,
linfangiogénesis y metástasis
(+ info)
Angiogenesis and permeability of blood vessels are regulated by vascular endothelial growth
factor (VEGF) via its two receptors VEGFR-1 and VEGFR-2. VEGFR-3 does not bind VEGF and
its expression becomes restricted mainly to lymphatic endothelia during development. We have
purified and cloned the VEGFR-3 ligand, VEGF-C. VEGF-C overexpression induces
lymphangiogenesis and growth of the draining lymphatic vessels, intralymphatic tumor growth
and lymph node metastasis in several tumor models. Furthermore, VEGFR-3 inhibitors bloc
lymphatic metastasis. These results together with recent clinical cancer studies indicate that
paracrine signal transduction between tumor cells and the lymphatic endothelium is involved in
lymphatic metastasis of human cancers. We have also recently found a role for VEGFR-3
signaling in settings of physiological and pathological angiogenesis in mice.
10:20
10:40
Café / Coffee
Francisco Real, CNIO, Madrid, Spain
Targeting the PI3K pathway in bladder cancer: different targets for different tumors?
/ La vía de PI3K en cáncer vesical: ¿dianas diferentes para tumores diferentes?
The PI3K pathway is involved in a wide variety of human cancers. In the bladder, there is
evidence for PI3K/mTOR activation in a large fraction of both non-muscle invasive and muscleinvasive tumors. PIK3CA mutations are very common in the former but they are rare in
muscle-invasive tumors. By contrast, PIK3CA gains and PTEN losses are rare in low grade,
non-muscle invasive, tumors and common in muscle-invasive cancers. It is crucial to
determine whether different genetic alterations have a differential effect on sensitivity to drugs
targeting PI3K/mTOR for rational clinical trial design.
(+ info)
11:20
Jonathan Yingling, Lilly Research Labs, Eli Lilly & Co. Corporate, Indianapolis, USA
Translating innovation: PK/PD driven drug discovery and patient tailoring in
oncology / Aplicando la innovación: descubrimiento de drogas en oncología a través
de PK/PD y adaptación al paciente individual
The pharmaceutical industry finds itself at a crossroads that requires transformational
approaches to meet the ever-increasing needs of patients, providers and payors. The
emergence of genomic technology has fundamentally changed oncology drug discovery and
provided unprecedented opportunities for new target discovery and validation as well as
“tailoring” to optimize patient outcomes. I will highlight the Lilly oncology strategy for
capitalizing on these breakthroughs and present 2 specific examples of portfolio assets that
have moved forward into the Lilly development pipeline and have the potential to significantly
improve the treatment of cancer.
SESIÓN 5
12:00
MicroRNAs AND EPIGENETICS / MicroRNAs Y EPIGENÉTICA
Chairperson / Moderador: Hernán Cortés Funes, Hospital 12 de Octubre, Madrid, Spain
Manel Esteller, Instituto de Investigaciones Biomédicas de Bellvitge (IDIBELL), Barcelona,
Spain
Cancer Epigenetics: from the bench to the bedside / Epigenética del cáncer: del
laboratorio a la cabecera del paciente
Cancer is an epigenetic disease characterized by the breakdown of the DNA methylation and
histone modification patterns. The stability of our genome and correct gene expression are
maintained in large measure thanks to a perfectly pre-established pattern of DNA methylation
and histone modifications. Both of them control the activity of a third component of the
epigenetic landscape, non-coding RNAs, particularly microRNAs that are also disrupted in
human cancer.
(+ info)
12:40
Jean-Pierre Issa, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Epigenetic therapy: from promise to reality / Terapia epigenética: desde la promesa a
la realidad
Over the past decade, epigenetic changes such as alterations in DNA methylation and histone
modifications have been well described in cancer and are now recognized as targets of therapy
(epigenetic therapy). The aim of epigenetic therapy is to reverse epigenetic changes and
reactivate important genes thereby modifying the malignant phenotype and inducing clearance
of the malignant clone by various mechanisms. DNA methylation inhibitors and histone
deacetylase inhibitors have already shown impressive activity in subsets of patients with
leukemia. The field is moving forward into solid tumors, and in parallel, other epigenetic targets
are being identified and targeted with drugs.
(+ info)
13:20
Reuven Agami, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Cancerous microRNAs and regulatory RNA binding proteins / MicroRNAs en cáncer y
proteínas reguladoras de RNA-binding
(+ info)
MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein coding genes.
Patterns of mis-expression of miRNAs in cancer suggest key functions of miRNAs in
tumorigenesis. In the past we set up experiments to identify miRNAs and identified miR-372,
miR-221 and miR-135 families as promoting tumor growth and metastasis. These miRNAs are
oncogenes as they are deregulated in various types of cancers, target tumor suppressors and
their inhibition reverts cancerous phenotypes. Interestingly, little is known about the
mechanisms controlling the expression and activity of miRNAs. This regulation is of outmost
importance due to the role miRNAs have during normal development and tumor progression.
Close inspection of miRNA-target sites on mRNAs revealed to us that occasionally sequences in
their vicinity are highly conserved throughout evolution. We therefore hypothesized that
conserved regions in mRNAs may serve as docking platforms for modulators of miRNA activity.
This led us to hypothesize that RNA-binding proteins could influence miRNA function. Modes of
this regulation will be discussed in this meeting.
POSTERS SESSION
14:00
SESIÓN 6
15:30
Almuerzo / Lunch
TARGETED THERAPY, EXAMPLES / TERAPIA DIRIGIDA A DIANAS, EJEMPLOS
Chairperson / Moderador: Eduardo Díaz Rubio, Hospital Clínico San Carlos, Madrid, Spain
Pierre Laurent-Puig, INSERM U775, Université Paris-Descartes, Paris, France
Prognostic factor in patients with advanced colorectal cancer treated with cetuximab
/ Factor pronóstico en pacientes con carcinoma colorrectal avanzado tratado con
cetuximab
We recently enlightened the role of the KRAS oncogene mutation as a marker of the resistance
to EGFR antibodies. The presence of KRAS mutations was significantly associated with an
absence of response to anti-EGFR monoclonal-antibody-based treatments. They are now
restricted to patients with a tumor with a non-mutant KRAS gene. However, only 50% of the
patients in this latter group give an objective response and other markers bring new
informations.
(+ info)
16:10
Josep Baselga, Vall d’Hebrón Hospital, Barcelona, Spain
Targeting HER2 in Breast Cancer. Novel therapies and mechanisms of resistance /
Apuntando a HER2 en cáncer de mama. Nuevos tratamientos y mecanismos de
resistencia
Aberrant receptor expression and/or functioning of the human epidermal growth factor receptor
(HER) family plays a critical role in the development and evolution of cancer. Inhibiting the
signalling activity of individual receptors in this family has advanced the treatment of a variety
of human cancers. In my presentation I will re-evaluate the role of two critical family
members, HER2 and HER3, and explore the mechanisms of action and preclinical/clinical data
for new therapies targeting signalling through these pivotal receptors. These new therapies
include tyrosine kinase inhibitors, antibody–chemotherapy conjugates, heat shock protein
inhibitors and antibodies that interfere with HER2:HER3 dimers.
(+ info)
16:50
Maria S. Soengas, CNIO, Madrid, Spain
Therapeutic windows for melanoma treatment / Ventanas terapéuticas para el
tratamiento del melanoma
(+ info)
17:30
Melanoma progression is invariably associated with multiple defects in apoptotic pathways. This
knowledge provides the platform for rational drug design. However, genetically targeted
therapies have not yet been proven effective in vivo. Therefore, melanomas may possess yet
unidentified mechanisms of cells survival. We have recently identified new roles of autophagy
(self cannibalism) underlying melanoma chemoresistance. Here we will report the
characterization of compounds able to rewire autophagy programs in melanoma cells to inhibit
tumor progression selectively (i.e. without affecting the viability of normal cell compartments).
We will present cellular and animal models that support selective autophagy induction as a
therapeutic window for intervention in melanoma.
Manuel Hidalgo, Centro Integral Oncológico Clara Campal (CIOCC), Madrid, Spain
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors / Inhibidores de
la tirosina-kinasa del receptor del factor de crecimiento epitelial (EGFR)
1 Review Current Status of EGFR Biology
2 Review State of the International Clinical Applications
3 Summarize New Agents and Therapeutic Strategies
(+ info)
18:10
Despedida y Clausura / Farewel & Closure
INFORMACIÓN GENERAL
− Conferencias: 30-minute talks; 10-minute discussion after each talk. English <> Spanish simultaneous translation.
− Posters: Permanent exhibition, attended by the authors at least on designed time periods / Exhibición permanente,
atendidos por los autores al menos durante las horas señaladas.
PROMOTORES Y PATROCINIO
COMITÉ CIENTÍFICO Y ORGANIZADOR
LUGAR DE CELEBRACIÓN
Miguel A Piris, Manuel Morente y José A Gutiérrez-Fuentes
EUROFORUM INFANTES
SAN LORENZO DE EL ESCORIAL, MADRID
Fundación Lilly: C/ María de Molina 3, 1º – 28006 Madrid – 91 781 50 70 - Fax 91 781 50 79 –
Email: fundacionlilly@lilly.com - www.fundacionlilly.com
Secretaría y apoyo logístico: Ana Isabel Moreno - Grupo 7 Viajes (c/ Medea 4, 3º A - 28037 Madrid)
Tel: 902 902 747 ext. 2 / Fax: 91 754 32 00 / anaisabel@grupo7viajes.com