Cancer Research in Switzerland - Krebsliga Schweiz

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156 Riggi Nicolò | BIL KFS 02717-08-2010 | CHF 88,400.– The role of microRNAs in Ewing’s sarcoma cancer stem cells Zielort: Institut universitaire de pathologie de Lausanne (IUP), Centre hospitalier universitaire vaudois (CHUV), Lausanne Sùva Mario | BIL KFS 02590-02-2010 | CHF 104,300.– Role of the polycomb group protein EZH2 in glioblastoma cancer stem cells Zielort: Harvard Medical School, Massachusetts General Hospital, Boston, USA Wirth Johann Gregory | BIL KLS 02593-02-2010 | CHF 41,000.– Apoptosis resistance in prostate cancer, with a focus on the use of patient tissue samples Zielort: Harvard Medical School, Massachusetts General Hospital, Boston, USA Clinical research Presentation of approved research projects in 2009/2010 Aebi Stefan | IBCSG39-10/MA.32: A phase III randomized trial of the effect of metformin versus placebo on recurrence and survival in early stage breast cancer (KFS 02689-08-2010) Duration: 01.09.2010 – 01.09.2013 A large clinical trial is investigating whether metformin, a drug used for the treatment of diabetes, diminishes the risk of recurrence in patients with early breast cancer. The trial was organized by the National Cancer Institute of Canada (NCIC) Clinical Trials Group. Swiss patients can participate through the International Breast Cancer Study Group. All patients will receive prophylactic (adjuvant) therapy according to current standards; this study aims to compare the frequency of relapses of patients on additional metformin with patients on standard therapy. Patients who consent will be randomly allocated to the control group or to the metformin group. In addition to the number of relapses, biological properties of the tumours will be studied (e. g. presence of insulin receptors) to find out which patients are most likely to respond to therapy. This trial will include 3,500 patients worldwide. It is being conducted by academic researchers without any funding from the pharmaceutical industry. This clinical trial will demonstrate whether a simple therapy with a well-known drug improves the prognosis of women with breast cancer. Project coordinator Prof. Dr. Stefan Aebi Medizinische Onkologie Luzerner Kantonsspital CH-6000 Luzern 16 Phone +41 (0)41 205 58 60 Fax +41 (0)41 205 58 62 Anderle Pedone Pascale | Exploiting transporters in the tumor-stroma interface to aim for a more efficient chemotherapy (OCS 02303-08-2008) Duration: 01.06.2009 – 01.06.2012 Tumour cells within the same carcinoma are heterogeneous and contribute to different aspects of tumour progression. Whereas some are mainly responsible for tumour growth and are in a proliferating state, others at the invasive front are responsible for invasion into the surrounding tissue. It has become clear in recent years that the behaviour of a tumour does not solely depend on the tumour cells alone but also on the interaction of the tumour cells with the surrounding tissue. However, still little is known on how tumour cells respond to their microenvironment. A better understanding of the underlying processes could eventually lead to improved therapy. In this project we are studying the expression and functions of membrane transporters that are known or very likely to be involved in tumour progression and may also serve as drug carriers. Using laser-dissection microscopy of tumour and healthy colon tissue from freshly operated patients, we will extract RNA to perform genome-wide profiling. Microarray expression data will be further validated with RT-PCR and protein expression patterns with immunofluorescence in human colon sections. Appropriate cell lines will be selected based on the gene expression profile and used for drug sensitivity and resistance testing. Eventually, we will test the effect of selected chemotherapeutics in vivo in mouse tumour models. In general, studying the tumour-stroma interaction is still an emerging field. In particular, the expression of transporters has hardly been studied in the context of tumourstroma interaction or in the context of the heterogeneity of a solid tumour. Thus, a better understanding of the role
of transporters with respect to chemosensitivity and chemoresistance in the various tumour cell subpopulations will contribute to a more efficient chemotherapy. Project coordinator Dr. Pascale Anderle Pedone Institut für Biochemie und molekulare Medizin Universität Bern Bühlstrasse 28 Postfach CH-3000 Bern 9 Phone +41 (0)31 631 47 39 Fax +41 (0)31 631 37 37 pascale.anderle@mci.unibe.ch Bertoni Francesco | Anaplastic large cell lymphoma: One or more entities? (KLS 02403-02-2009) Duration: 01.08.2009 – 01.08.2011 The recent 2008 World Health Organization (WHO) classification divides anaplastic large cell lymphoma (ALCL) into two distinct subgroups based mainly on the presence or absence of translocations affecting the anaplastic lymphoma kinase (ALK) gene. It is well accepted that patients with ALK positive ALCL are a distinct group sharing unique phenotypic and well-defined genetic and clinical features. Although the general clinical presentations and peculiar translocations and/or genetic events differ in the ALK positive and ALK negative ALCL subgroups, the question as to how related the two types of ALCL are and whether ALK negative ALCL may represent a subset of ‘peripheral T-cell lymphomas, not otherwise specified (PTCL, NOS)’ remains open. The aim of this project is to focus on the genetic events underlying the pathogenesis of ALCL. The dual aim is to provide better tools to differentiate the individual lymphoma types and to identify genes that might represent new therapeutic targets. Material and methods The study is being performed on a large series of ALK positive and ALK negative ALCL clinical samples; this has been made possible thanks to an international network of collaborating investigators. For genomic profiles we are using Affymetrix Human Mapping SNP6 Arrays and for gene expression profiling Affymetrix U133 plus 2.0. We are also data mining a very large dataset of proprietary and public T-cell NHL gene expression profiles. Results Ongoing are: data mining, validation of regions of interests and characterization of a gene identified by data mining of the gene expression profiles. The project is proceeding according to plan. Project coordinator Dr. Francesco Bertoni Laboratorio di oncologia sperimentale Istituto oncologico della Svizzera italiana (IOSI) Via Vincenzo Vela 6 CH-6500 Bellinzona Phone +41 (0)91 820 03 67 Fax +41 (0)91 820 03 97 frbertoni@mac.com Bourquin Jean-Pierre | Pre-clinical evaluation of a new pharmacological approach using obatoclax for chemosensitization of drug resistant childhood acute lymphoblastic leukemia (KFS 02453-08-2009) Duration: 01.03.2010 – 01.03.2011 Using a preclinical model that is based on representative cases with highly resistant disease, we have established a new rationale for chemosensitization in acute lymphoblastic leukaemia (ALL). A small molecule that is thought to act as an antagonist of critical regulators of programmed cell death, obatoclax mesylate, very effectively restored the response to conventional chemotherapeutic agents in ALL cells that were otherwise completely refractory to these conventional chemotherapeutic agents. Unexpectedly, combination of obatoclax with dexamethasone, one of the most important drugs for ALL treatment, triggered a new type of programmed cell death specifically in resistant leukaemia cells but not in chemosensitive ALL cells, providing a strong rationale for a selective therapeutic targeting of resistant leukaemia cells. Interestingly, combination of obatoclax with other cytotoxic agents triggered a classical cell death pathway, the mitochondrial apoptotic pathway, suggesting that this agent interferes with critical mechanisms at the interface of two cell death pathways. Based on our work, which is in part published in the Journal of Clinical Investigation, a proposal for a clinical phase I trial was developed under the auspices of the leading group of experts in Europe, regrouped in the resistant disease committee of the international BFM Study Group (BFM stands for Berlin-Frankfurt-Münster to credit the important contribution of the first founders who paved the way to successful chemotherapy regimen for ALL). The aim of this study is to evaluate toxicity and gain first evidence for activity of the combination of obatoclax and dexamethasone in patients with relapsed or refractory ALL. This approach would then be taken forward as an investigational phase II window for high risk patients in first relapse to evaluate clinical activity. This trial will also contribute to designing an experimental therapy with several chemotherapeutic agents for patients with refractory disease. This proposal has received a lot of attention in the field and was declared as one of the priorities for drug development for refractory ALL by IBFM. To further improve and accelerate the clinical development of obatoclax as chemosensitizer, we established a larger number of cases with relapsed and refractory B-cell precursor (BCP) and T-cell ALL using our leukaemia xenograft model. The aim was to understand whether resistance to chemosensitization with obatoclax could occur in this patient population and to identify biomakers that would help predict a response to the drug. Interestingly, we could not find any case that would not respond to the combination of obatoclax with chemotherapeutic agents in BCP-ALL but detected several resistant cases in T-ALL. Sensitization activity to the glucocorticoid drug dexamethasone using obatoclax was clearly associated with inhibition of mTOR kinase activity, an important signalling node that integrates signals from different pathways to promote tumour growth. We used our leukaemia xenograft model to test the possibility to follow mTOR kinase 157
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Cancer Research in Switzerland A pu
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Cancer Research in Switzerland
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Basic biomedical research 55 Cancer
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policy work and was in charge of de
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The main focus of the research fund
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gramme research funding decreased b
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Table 2 Distribution of funds for i
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Funding patient-centred research Pa
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value was not clearly discernible.
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New organization of the Foundation
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The board of the Foundation Cancer
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The president of the Scientific Com
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Prof. Martin Pruschy, PhD Departmen
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Swartz wants to find out how tumour
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The scientific and medical research
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3. The original order/sequence of t
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As a federation, the Cancer League
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List of funded research projects, i
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Zippelius Alfred | 2009: CHF 100,00
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Kridel Robert | 2010: CHF 100,000.-
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Thurgau Cancer League Biotechnologi
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Weller Michael | 2010: CHF 65,828.-
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manageable funding of individual pr
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enhances breast cancer cell motilit
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Rüegg Curzio et al. | Tumor-mediat
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International Clinical Cancer Resea
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in PHIV were shown for Hodgkin’s
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Zucca Emanuele et al. | Internation
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56 “hierarchical structure” of
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58 the attempt should be made to st
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60 Gönczy Pierre | KLS 0202402
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62 Romero Pedro | OCS 020110220
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64 Beermann Friedrich | In vivo scr
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66 Christofori Gerhard | Podoplanin
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68 Frei Christian | The function of
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70 cell, this novel mechanism serve
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72 Results The induction of viral p
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74 Hübscher Ulrich | Repair of oxi
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76 Methods and experimental approac
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78 of cMyc and/or NMyc and demo
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80 In summary, this work improves o
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82 Pruschy Martin | Microtubule int
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84 Renner Christoph | Selective inh
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86 Goal Here we build on these obse
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88 by TDG prevents efficient downst
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90 To address these questions, we a
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92 Translational relevance The resu
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94 Grünberg Jürgen | KFS 025460
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96 Tschan Mario P. | KFS 0248608
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98 Boyman Onur | Preclinical testin
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100 Constam Daniel | Role of activi
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102 this study we will examine the
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104 Janscak Pavel | Study of the ro
Page 108 and 109: 106 Müller Anne | The molecular pa
Page 110 and 111: 108 Radtke Freddy | The role of Not
Page 112 and 113: 110 Schär Primo | DNA repair, epig
Page 114 and 115: 112 In this project we will investi
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Page 118 and 119: 116 and Research). Other financial
Page 120 and 121: 118 be totally unaffordable for aca
Page 122 and 123: 120 Clinical research List of compl
Page 124 and 125: 122 Hunger Robert E. | OCS 02262-08
Page 126 and 127: 124 Clinical research Presentation
Page 128 and 129: 126 Benhattar Jean | Identification
Page 130 and 131: 128 Bertoni Francesco | Genome-wide
Page 132 and 133: 130 Interpretation ESA treatment in
Page 134 and 135: 132 Our results could pave the way
Page 136 and 137: 134 new drugs that specifically tar
Page 138 and 139: 136 slides in two different concent
Page 140 and 141: 138 Conclusions A strong network of
Page 142 and 143: 140 tions introduced to ARE motifs
Page 144 and 145: 142 Müller Beatrice U. | The maste
Page 146 and 147: 144 A novel method was developed fo
Page 148 and 149: 146 (SAKK 35-98) the Swiss Group fo
Page 150 and 151: 148 Timmermann Beate | Prospective
Page 152 and 153: 150 recurrence of the disease, we a
Page 154 and 155: 152 Zucca Emanuele | A prospective
Page 156 and 157: 154 Heinimann Karl | KFS 02489-08-2
Page 160 and 161: 158 activity at the single cell lev
Page 162 and 163: 160 Our research projects aim at un
Page 164 and 165: 162 Körner Meike | In vitro evalua
Page 166 and 167: 164 Nadal David | Is endemic Burkit
Page 168 and 169: 166 (> 50.000/patient). For their a
Page 170 and 171: 168 Zeller Rolf | Functional analys
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Page 174 and 175: 172 area of health services researc
Page 176 and 177: 174 The financing of palliative car
Page 178 and 179: 176 National Strategy for Palliativ
Page 180 and 181: 178 Psychosocial research List of c
Page 182 and 183: 180 Within the patient group, level
Page 184 and 185: 182 Further, the results suggest th
Page 186 and 187: 184 It is in this context that the
Page 188 and 189: 186 Recommendation Female spouses o
Page 190 and 191: 188 Psychosocial research Presentat
Page 192 and 193: 190 rates communication skills rema
Page 195 and 196: Epidemiological research Epidemiolo
Page 197 and 198: data from cancer registries. In the
Page 199 and 200: The importance of cancer registries
Page 201 and 202: Ess Silvia | Patterns of care and s
Page 203 and 204: Epidemiological research List of ap
Page 205 and 206: Impact This work will serve as the
Page 207 and 208: Thürlimann Beat | Management of br
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Cancer Research in Switzerland - Krebsliga Schweiz

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