INFRAFRONTIER Conference 2020

Targeting Cancer with Animal Models

October 7 to 8, 2020      Virtual Conference

Please note: Due to the COVID-19 pandemic, the conference has been rescheduled to 07 - 08 October and moved online completely. This site has been updated accordingly. 




Registration deadline: October 2, 2020

After cardiovascular diseases, cancer is the leading cause of death and one of the major contributors to premature deaths in the EU. In 2016, one quarter (26.0%, 1.3 million people) of the total number of deaths in Europe were due to cancer and it was predicted to kill 1.41 million in 2019. The EC has taken a strong stand in the fight against cancer with the inception of its Europe Beating Cancer Plan and the Cancer Mission area for the Horizon Europe framework beginning in 2021. The Cancer Mission is guided by experts from various facets of cancer treatment like cancer research, innovation, policy, healthcare provision and practice. These experts constitute the Cancer Mission Board. 

With recent biomedical advances it has become obvious that cancer is not a single disease but a collection of several diseases. What these maladies have in common is the uncontrolled growth of cells disrupting the delicate balance between life and death; proliferation and apoptosis. Cancer research and treatment are particularly challenging because tumours exhibit different tumour origins and mechanisms for subverting the natural cellular checkpoints for survival, death, immune evasion, drug sensitivity and metastatic invasion. To further complicate matters, this heterogeneity is also prevalent among cells of the same tumor. Thus, the treatment of cancers requires a more personalised approach customised towards a particular tumours genetic and cellular perturbations. 

Mouse models are used in cancer research to explore the causality between cancer genes and carcinogenesis, and as models to develop and test novel therapies. In addition, they have become ideal models for precise individualized cancer therapy thanks to the advancements in CRISPR/Cas9-mediated genome editing, patient xenograft implantation and microbiota studies enabling them to effectively replicate the aforementioned cancer heterogeneity in a laboratory setting. 

The INFRAFRONTIER Conference 2020 ‘Targeting Cancer with Animal Models’ aimed to showcase such innovative animal models used in cancer research and also introduced the Cancer Mission Board to the cancer research community. 

The main objectives of this conference was to:

  • Present latest research on innovative cancer models
  • Showcase INFRAFRONTIER services for cancer research
  • Align the scientific strategy on cancer mouse models with the Horizon Europe Cancer Mission





 Conference Agenda

Download the agenda here.

OCTOBER 7, 2020

SESSION 1 - Innovative in vivo and in vitro Models in Cancer Research

Chair: Martin Hrabĕ de Angelis, Helmholtz Center Munich / INFRAFRONTIER, Germany

***Note: All times are Central European Summer Time (CEST)

13:00 - 13:15 

Welcome and Introduction


Martin Hrabĕ de Angelis

Helmholtz Center Munich / INFRAFRONTIER, Germany

13:15 - 14:00

Keynote: Crossing the Valley of Death: The Need for Better Preclinical Mouse Tumor Models 

Hellmut G Augustin1,2,3 and co-workers

1 Division of Vascular Oncology and Metastasis Research, German Cancer Research Center Heidelberg, Germany

2 European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Germany

3 German Cancer Consortium, Heidelberg, Germany


The availability of advanced preclinical tumor models is rate limiting for both, the advancement of basic tumor biology as well as for translational oncology research. This situation is increasingly aggravating at a time when cancer is no longer perceived as a local disease, but rather requires consideration of the systemic nature of tumors for which experimental model systems are hardly established. A recent meta-analysis of published studies has revealed that the vast majority of contemporary preclinical mouse tumor model research is still based on reductionist grafted cell line models. In turn, there is a whole plethora of sophisticated genetically-engineered mouse models (GEMM), patient-derived xenograft models (PDX) as well as natural cause tumorigenesis models that are capable to effectively mimic human tumors in the preclinical setting. Yet, most of these models are not sufficiently versatile to eventually serve as widely used flagship models. Moreover, lack of model standardization, missing SOPs and questionable data presentation and analysis limit a seamless translational bench-to-bedside process. This presentation reviews the current state-of-the-art of contemporary preclinical tumor model research, discusses some major bottlenecks and proposes a platform of GEMM-derived syngraft models and novel focal surgical GEMM models (for metastasis research) that could contribute to overcoming some of the current limitations and bottlenecks.

Hellmut Augustin

German Cancer Research Centre (DKFZ), Germany

14:00 - 14:20
Genetic dissection of breast cancer development, therapy response and resistance in mouse models

Jos Jonkers, Netherlands Cancer Institute, Amsterdam, The Netherlands  

Our research is focused on the genetic dissection of human breast cancer through the use of genetically engineered mouse models and patient-derived tumor xenograft models. For this, we have developed mouse models for BRCA1- and BRCA2- associated hereditary breast cancer and E-cadherin mutated invasive lobular carcinoma (ILC). We have used these models to (1) investigate genotype-phenotype relations in mammary tumorigenesis; (2) identify genetic changes underlying breast tumorigenesis; (3) study mechanisms of therapy response and resistance.

Our mouse models for BRCA1-deficient breast cancer develop tumors that are characterized by genomic instability and hypersensitivity to DNA-damaging agents and PARP inhibitors. Nevertheless, none of these drugs are curative: tumors grow back after drug treatment and eventually become resistant. Using a combination of functional in vitro screens and in vivo studies, we have found that therapy resistance of BRCA1-mutated tumors can be induced by several mechanisms, including genetic reversion, activation of drug efflux transporters, hypomorphic BRCA1 activity, and rewiring of the DNA-damage response.

Using forward and reverse genetics in our mouse models of ILC, we have shown that mutations in fgfr2or PI3K pathway components (pik3ca, Akt or Pten) strongly cooperate with E-cadherin loss in tumorigenesis, leading to development of mammary tumors that closely resemble classical ILC. We have also rebalancing actomyosin contractility in mammary epithelial cells that have lost E-cadherin is critically required for ILC development.

To accelerate in vivo evaluation of candidate drivers and drug resistance genes, we have developed novel methods for rapid generation of germline and non-germline breast cancer models. Using embryonic stem cells (ESCs) derived from our conditional mammary tumor models, we can quickly introduce additional gain- and loss-of-function alleles and generate novel tumor models by blastocyst-injection of the manipulated ESCs. Using intraductal injection of CRISPR vectors in mammary tumor models with conditional expression of Cas9, we can test candidate tumor suppressors by in vivo gene editing.

Jos Jonkers

Netherlands Cancer Institute (NKI), Netherlands

14:20 - 14:40
Lysosomal membrane: Achilles heel of glioblastoma cells

Pirjo Laakkonen PhD, Translational Cancer Medicine Research Program, Faculty of Medicine, and Laboratory Animal Centre, HiLIFE Helsinki Institute of Life Science, University of Helsinki, Finland

Glioblastomas are the most frequent, aggressive and lethal brain tumours in adults with 5-year survival rate less than 3%. These diffusive tumours spread widely within the brain parenchyma, making the surgical removal impossible. So far, therapies have been challenged by their lack of specificity, inability to reach the brain due to the blood-brain-barrier or impossibility to prevent the tumour relapse. Targeting the cancer cell lysosomes to trigger lysosomal leakage is an idea that emerged over the past decade. Once damaged, lysosomes release their proteolytic content into the cytoplasm, leading to the rapid destruction of the cell through a mechanism defined as lysosomal membrane permeabilization (LMP). Even though this cell death mechanism has been known for some time no genes or pathways involved in LMP have been unravelled until our study.

We discovered that the invasive glioblastoma cells are unexpectedly sensitive to the LMP. While dissecting the molecular mechanism underlying the LMP, we identified a glioma-specific gene, FABP3, to be essential for the stabilization of the lysosomal membrane via transport of polyunsaturated lipids needed for lysosomal biogenesis. Genetic depletion of FABP3 leads to deleterious modifications of the lipid contents of the lysosomal membrane, leading to their leakage and glioblastoma cell death.

In order to take advantage of the glioma cell’s lysosomal weakness, we searched for compounds capable of inducing the LMP and also able to cross the blood-brain-barrier in vivo. We found that cationic amphiphilic molecules, such as the antihistamine clemastine, can accumulate in the lysosome and destabilize their membrane leading to the cell death by LMP. We demonstrate that daily peripheral dosage of clemastine is capable of destructing all invasive glioma cells within the central nervous system, in several patient-derived xenograft models. Our study therefore supports the repurposing of the FDA-approved cationic amphiphilic drugs, as a potential therapeutic support to eradicate invasive gliomas.

Pirjo Laakkonen

Helsinki Insitute of Life Science (HiLIFE), Finland

14:40 - 15:00
Absence of mouse‑driven genomic evolution during engraftment and propagation of patient-derived cancer xenografts

Enzo Medico, University of Torino and Candiolo Cancer Institute, Candiolo, Italy; EurOPDX Consortium.


Patient-Derived Xenografts (PDXs) are preclinical models largely used to study tumor biology and drug response. Recent literature highlighted the possibility that growth of human tumours in a mouse microenvironment imposes a selection driving mouse?specific genetic evolution of PDXs, which may compromise their reliability as human cancer models. Conversely, independent studies observed a conservation of the genomic landscape during PDX engraftment and passaging. We resolved these contradicting observations by systematically evaluating copy number alteration (CNA) changes and the genes they affect during engraftment and passaging in a large series of PDX models. CNA data generated and collected by the EurOPDX consortium and the PDXNet Consortium comprised 1548 patient (PT) and PDX datasets (1451 unique samples) from 509 models derived from American, European, and Asian cancer patients, spanning across 16 tumor types. Assessment of CNA changes by pairwise (PT-PDX or PDX-PDX) correlation and residual analysis to control for systematic biases confirmed high retention of the CNA profile during PDX engraftment and passaging.

We further analysed CNA profiles of 87 colorectal and 43 breast cancer triplets, each composed of matched patient’s tumor (PT) and PDX at early (PDX?early) and later (PDX-late) passage. In this way, for each tumor type, we generated three perfectly matched PT, PDX-early and PDX-late cohorts and performed CNA recurrence analysis by GISTIC in each cohort. The hypothesis was that if the mouse host induces a selective pressure capable of shaping the CNA landscape during PDX engraftment and propagation, GISTIC analysis would highlight systematic and progressive changes, from the PT to the PDX-early cohort, and then to the PDX-late cohort. Notably instead, the CNA profiles of the PT and PDX-early/late cohorts were virtually indistinguishable, with no progressive accumulation or loss of CNA during PDX passage and only minor changes not functionally related or associated to cancer-driver or actionable genes. Interestingly, we found that a major contributor to the differences between PDX samples is lineage-specific drift associated with splitting of tumours into fragments during PDX propagation. In summary, our systematic analysis of DNA-based CNA profiles excluded a systematic mouse driven selection via copy number changes, thus supporting the robustness of PDXs as preclinical models for predicting drug response.

Enzo Medico

University Of Turin (UniTO), Italy

15:00 - 15:30Coffee Break 
15:30 - 15:50
Cyclooxygenase 2-driven inflammation in pancreatic cancer

Chiblak, Sara1, Gräbner, Rolf2, Habenicht, Andreas2, Giese, Nathalia3, Büchler, Markus3, Fürstenberger, Gerhardt1, and Müller-Decker, Karin

1German Cancer Research Centre, Heidelberg, Core Facility Tumor Models, Heidelberg,Germany; 2,Friedrich-Schiller-University, Institute for Vascular Medicine, Jena, Germany, 3Ruprecht-Karls- University, Department of Surgery, Heidelberg, Germany. Contact:


The cause-effect relationship between over-expression of pro-inflammatory cyclooxygenase (COX)-2, COX-2-mediated prostaglandin (PG) signaling and the development of epithelial cancers is universally accepted. Depending on the cellular context, PG stimulate growth, angiogenesis, and modulate immune functions in inflammation-driven cancers. Keratin 5 promoter-driven COX-2 (K5 COX-2) transgenic mouse lines develop pre-invasive neoplasms in various epithelial tissues including ductal pancreatic neoplasms, which resemble human precursor lesions of pancreatic ductal adenocarcinoma (PDAC), i.e. cystic intra-ductal papillary mucinous neoplasms and pancreatic intra-epithelial neoplasias. These phenotypic changes are associated with pronounced inflammatory infiltrates. Gene expression analysis points to a significant synthesis of TLO (ectopic tertiary lymphoid organs)-relevant cytokines. At the cellular level, in the diseased pancreata diffuse inflammatory infiltrates are observed besides prominent inflammatory clusters. These are comprised of B-cells, T-cells, follicular dendritic cells, macrophages, and high endothelial venules decorated with lymphocyte adhesion molecules, altogether known as hallmarks of TLO, which arise in chronic inflammatory diseases but with a still poorly characterized function. In addition, typical chemokines such as CXCL13, lymphotoxin-beta, and CCL19 are expressed. Such an inflammatory phenotype is suppressed by inhibition of COX-2 activity whereby celebrex-fed transgenics exhibit fewer and smaller clusters, indicating the involvement of COX-2 in the establishment of TLO; a putative novel COX-2-effect on local immunity. Follicular clusters rich in B- cells and T-cells, with vessels that express peripheral lymph node addressin are also observed in COX-2-positive human PDAC. Published clinical data suggest that TLO do not represent a high-risk environment and are associated with a comparably good prognosis in human PDAC.

Karin Müller-Decker

German Cancer Research Centre (DKFZ), Germany

15:50 - 16:10 
Tumour organoid cultures as a platform for functional genomics

In an era of genomics-guided precision medicine there is an increasing need for models that reflect the hallmarks of cancer and the molecular diversity of patient tumours. New cell culturing methods are transforming our ability to derive cell models from healthy and diseased tissues, with increased success rates, and linked to patient genomic and clinical data. I will update on our efforts as part of the Human Cancer Models Initiative (HCMI) to create a new biobank of molecularly-annotated tumour organoids as a community resource. Furthermore, I will present how we are beginning to use these organoid cultures for chemical and genetic screen to identify new molecular targets and biomarkers of therapy response. These early studies are laying the foundation for a next-generation tumour organoid functional genomics platform to help guide the development of future precision cancer medicines.

Mathew Garnett

Wellcome Sanger Institute, United Kingdom

16:10 - 16:30
Development of a human RANKL-driven mouse model of mammary carcinogenesis

Ntari, Lydia1; Christodoulou-Vafeiadou, Eleni1; Kolokotroni, Anthi2; Papanastasiou D, Anastasios3; Rouchota, Maritina4; Loudos, George4; Douni, Eleni2,5, Denis C, Maria1, Karagianni, Niki1

1 Biomedcode Hellas SA, Vari, Greece

2 Insitute of Biodivision, Biomedical Sciences Research Center “Alexander Fleming”, Athens, Greece

3 Department of Biomedical Sciences, University of West Attica, Athens, Greece

4 Bioemission Technology Solutions (BIOEMTECH), Lefkippos Attica Technology Park, NCSR “Demokritos”, Greece

5 Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Athens, Greece

* e-mail:


Breast cancer is the most frequent and highest lethality-causing cancer among women worldwide, as existing treatments remain inadequate. Therefore, the need to develop new personalized targeted treatments is vital.


RANKL(receptor activator of NF-?B ligand) protein and its receptor RANK have been shown to play a significant role in the initiation and development of breast cancer in mice, in addition to their known role in bone homeostasis1, thus offering an attractive therapeutic target of mammary carcinogenesis. In order to study further its role and its therapeutic potential in breast cancer, we induced progesterone-driven carcinogenesis1 in mice that overexpress human RANKL protein together with its mouse counterpart(TghuRANKL)2, as well as mice that explicitly express human RANKL in the absence of functional mouse RANKL(TghuRANKL/RANKLtles/tles)3. Nine-to-fifteen weeks following induction, all mice developed palpable tumours, that were analysed clinically as well as histopathologically. Clinical analysis included in vivo tumour measurements and whole-body imaging, using live positron emission tomography scanning(?-eyeTM,BIOEMTECH). Histopathological analysis included immunohistochemistry as well as evaluation of tumour characteristics in H/E-stained slides. Tumour initiation and development in WT and TghuRANKL mice was ameliorated following treatment with an anti-RANKL inhibitor blocking both mouse and human RANKL, while mammary carcinogenesis was almost completely prevented following treatment with the commercially available anti-huRANKL denosumab.


Collectively, we present a human RANKL-driven mouse model of mammary carcinogenesis that can be used as basis for the development of an evaluation tool for huRANKL-targeted therapeutics, as well as for downstream targets of its signalling cascade with a role in breast cancer biology.

Bibliography 1. Schramek et al. Nature (2010), 468:7320 2. Rinotas et al. Journal of Bone and Mineral Research (2014), 29 (5): 1158–1169 3. Douni et al. Human Molecular Genetics (2012), 21:784–98

Lydia Ntari

Biomedcode, Greece

16:30 - 16:50
Imaging tumor acidosis in preclinical murine tumor models

Longo, Dario Livio1, Anemone, Annasofia2, Corrado, Alessia1, Carella, Antonella1, Villano, Daisy2, Zullino, Sara2, Aime, Silvio2

1 National Research Council of Italy (CNR), Institute of Biostructures and Bioimaging (IBB), Torino, Italy

2 University of Torino, Department of Molecular Biotechnologies and Health Sciences, Torino, Italy

Non-invasive imaging techniques are playing a fundamental role in cancer research, allowing to investigate tumor microenvironment, interactions between host cells and to monitor response to treatment both at preclinical and clinical level [1]. The need for advanced imaging techniques is tackled by the EuroBioImaging Research Infrastructure by offering access to cutting-edge technologies for biomedical imaging to life-science researchers [2].

Among the dysregulated tumor physiological properties, increased glycolysis and hypoxia lead to enhanced acidification of the tumor extracellular pH (pHe) to values in the range 6.5-7.0, which is a salient feature of the tumor microenvironment. However, despite tumor acidosis is now considered an hallmark of cancer, imaging-based methods are not yet fully and widely available to interrogate the acidic microenvironment.

We have developed innovative MRI-based approaches for imaging in vivo tumor acidosis that can be exploited for evaluating its relationship with cancer metabolism and metastatic potential as well as for assessing treatment response to novel anticancer therapies [3,4].

Based on the reported findings, tumor pH imaging is emerging as an innovative diagnostic tool for characterizing tumor metabolism and to evaluate treatment response translatable to the clinics.

References [1] Glunde K, Pathak AP, Bhujwalla ZM. Molecular-functional imaging of cancer: to image and imagine. Trends Mol Med. 2007,13:287-97. doi: 10.1016/j.molmed.2007.05.002


[3] Anemone A, Consolino L, Arena F, Capozza M, Longo DL. Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH. Cancer Metastasis Rev. 2019, 38:25-49. doi: 10.1007/s10555-019-09782-9

[4] Consolino L, Anemone A, Capozza M, Carella A, Irrera P, Corrado A, Dhakan C, Bracesco M, Longo DL. Non-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging. Front Oncol. 2020, 10:161. doi: 10.3389/fonc.2020.00161

Dario Longo

Institute of Biostructures and Bioimaging (IBB)

Italian National Research Council (CNR), Italy


OCTOBER 8, 2020

SESSION 2 - Stakeholder Talks

Chair: Valerie Gailus-Durner, German Mouse Clinic / INFRAFRONTIER, Germany

           Sabine Fessele, INFRAFRONTIER GmbH, Germany


09:00 - 09:45
Keynote: Investigating cancer immunotherapies using mouse models

Malissen Bernard, Luche Hervé, Malissen Marie and Zarubica Ana Centre d’Immunophénomique, PHENOMIN-CIPHE, Marseille, France


The possibility to edit the mouse genome and to profile the immune system of the resulting mouse models has permitted many discoveries in cancer treatment and immunotherapy, including the anti-tumor effects of CTLA-4 and PD-1 blockade. Moreover, mouse models provide the unique possibility to establish causal relationships under in vivo physiological conditions. For instance, it is presently possible to track and ablate in vivo most of the cell types involved in innate and adaptive immunity. This possibility will be exemplified using a subset of dendritic cells that plays a key role in tumor immunity by helping T cells to target tumors. However, some features of human cancer immunobiology are not fully reflected by current mouse models. For instance, the immune system of laboratory mice kept under SPF conditions more closely resembles that of neonatal humans, while co-housing laboratory mice with ‘dirty’ mice ‘humanizes’ their T cell population profiles to mimic that of adult humans. As will be outlined, CIPHE has the ability to develop genetically engineered mouse models under SPF/SOPF conditions including mice with humanized checkpoint molecules and well-characterized syngeneic models. CIPHE can also phenotype their immune system under normal and pathological conditions (inflammation and cancer) using advanced multiparametric flow, mass, and spectral cytometry. To more accurately mimic the complexity of the human tumor microenvironment, CIPHE has acquired the Hu-Mice technology (hemato-lymphoid humanised mice) via a strategic partnership and combines it with its expertise in high-content immunoprofiling to further our knowledge in human immunobiology and oncology.

Bernard Malissen

Centre d’Immunologie Marseille-Luminy (CIML), France

09:45 - 10:05
Intravital multiphoton microscopy in a syngeneic melanoma mouse model unravels a translationally relevant role for connexin hemichannels in cancer photodynamic therapy

Nardin Chiara, Peres Chiara, Putti Sabrina, Orsini Tiziana, Salvatore Anna Maria, Tettey-Matey Abraham, Chiani Francesco, Scavizzi Ferdinando, Raspa Marcello and Mammano Fabio*

CNR Institute of Biochemistry and Cell Biology, INFRAFRONTIER/IMPC Group, Monterotondo, Italy

Malignant melanoma, the most aggressive skin cancer, develops high resistance to conventional therapies in the metastatic stage, is associated to a poor patient prognosis and its frequency of occurrence in the population has been constantly increasing over the past several decades [1]. Photodynamic therapy (PDT) is a consolidated and minimally invasive treatment. It requires assimilation by tumor cells of photosensitizer (PS) molecules that remain inert and non-toxic until excited by light. Tumor-loaded and light-activated PS molecules trigger cascades of highly cytotoxic reactive oxygen species (ROS) [2]. Here, to track PDT effects in real time, we performed intravital multiphoton microscopy in syngeneic melanomas grown in the mouse dorsal skinfold chamber (DSC) preparation [3] and loaded with a PS (Aluminum Phthalocyanine Chloride). PS photo-activation elicited intercellular Ca2+ waves that were dependent on purinergic P2Y receptors and passed from irradiated to non-irradiated/bystander cells promoting inter-organelle Ca2+ transfer and activation of apoptotic pathways. We discovered that connexin hemichannel (HC) activity associated to ATP release was a key component of PDT-mediated bystander cell killing, which could be enhanced by chelating extracellular Ca2+ to favor HC opening. These pre-clinical findings in a syngeneic melanoma mouse model are translationally relevant: they demonstrate paracrine signaling mediated by connexin HCs can be exploited to improve treatment of melanoma, and possibly other tumors as well. Keywords Ca2+ waves, ATP release, purinergic signaling, bystander effect, reactive oxygen species, endoplasmic reticulum, mitochondria. References [1] A.M. Forsea, Melanoma Epidemiology and Early Detection in Europe: Diversity and Disparities, Dermatol Pract Concept, 10 (2020) e2020033. [2] A.P. Castano, T.N. Demidova, M.R. Hamblin, Mechanisms in photodynamic therapy: part one-photosensitizers, photochemistry and cellular localization, Photodiagn Photodyn, 1 (2004) 279-293. [3] M.W. Laschke, B. Vollmar, M.D. Menger, The dorsal skinfold chamber: window into the dynamic interaction of biomaterials with their surrounding host tissue, European cells & materials, 22 (2011) 147-164.

Fabio Mammano

Institute of Biochemistry and Cell Biology (CNR), Italy

10:05 - 10:25

Mapping modifiers for different cancer developments in collaborative cross mice

Department of Clinical Microbiology & Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Tel-Aviv, Israel



A number of genetic modifier loci for different cancers were previously mapped, but so far, most of the underlying genes have not been identified. The Collaboratoive Cross (CC) genetic reference population is, the next generation of mouse genetic reference population, allows time and cost-efficient mapping of target regions as quantitative trait loci (QTLs) that are responsible for the genetic variance of a specific complex trait. The CC is a large panel of recombinant inbred (RI) strains derived from a genetically diverse set of eight founder strains and designed specifically for complex trait analysis and power than any reported approaches. In order to identify modifier genes associated with cancer developments, we performed QTL analysis of cancer development using F1 crosses between mice of different CC lines, and mice carrying mutated suppressor cancer genes including; Adenomatous polyposis coli (APC) for intestinal cancer (IC) development, and Head and Neck Squamous Cell Carcinoma (HNSCC) and breast cancer. Males of C57BL/6Min and C57BL/6Smad4ko lines were crossed with females of different CC lines for developing F1 crosses, for studying IC and HNSCC, respectively. For IC project, F1 offspring were terminated at 23 weeks and polyp counts from three small intestinal and colon were recorded, separately. The number of polyps in all these sub-regions varied significantly between the different F1 crosses. Nine distinct and novel QTL at 90 and 95% genome-wide significant (GWS) thresholds levels, and at least additional 16 more QTL at 50% GWS were mapped. HNSCC and other cancers will be discussed at the conference.

Fuad Iraqi

Tel Aviv University, Sackler Faculty of Medicine, Israel

10:25 - 10:45

A rodent model of KIT-induced human cancer: Clinical and histopathological characterization

Rathkolb, Birgit 1,2,3, Klein-Rodewald, Tanja 1, Kraiger, Markus1, Micklich, Kateryna1, Calzada-Wack, Julia1, Sanz-Moreno, Adrián1, Fuchs, Helmut 1, Gailus-Durner, Valerie 1, Aigner, Bernhard 2, Wolf, Eckhard2, Hrabé de Angelis, Martin 1,3,4

1 Helmholtz Zentrum München, Institute of Experimental Genetics and German Mouse Clinic, Neuherberg, Germany

2 Ludwig-Maximilians-Universität München, Institute of Molecular Animal Breeding and Biotechnology, Munich, Germany

3 Member of the German Center of Diabetes Research, Neuherberg, Germany

4 Technische Universität München, Center of Life and Food Sciences Weihenstephan, Chair of Experimental Genetics, Freising-Weihenstephan, Germany


The c-kit gene plays a major role during differentiation and proliferation of several cell types and encodes the receptor tyrosine kinase KIT which mediates signaling of the stem cell factor. Activating KIT-mutations represent one possible primary cause of aggressive types of neoplasias, such as gastrointestinal stromal tumors (GIST), acute myeloid and mast cell leukemia (AML, MCL), melanoma as well as germ cell tumors and are also associated with several other types of cancer. The development of the KIT-specific tyrosine kinase inhibitor Imatinib significantly improved treatment options. However, a group of mutations associated with resistance to Imatinib treatment has been identified.


A novel ENU-induced mouse mutant, provisionally named MVD013, carrying the homologous mutation to an Imatinib-resistant mutation found in different types of human cancer in the murine Kit protein, was generated on a C3HeB/FeJ (C3H) genetic background during the Munich ENU Mouse Mutagenesis Project and characterized in the German Mouse Clinic. Heterozygous mutant animals showed initially permanent microcytic polycythemia, followed by age-related changes in differential blood counts, hyperproliferation of gastrointestinal stromal cells associated with disturbed ingesta transport and in females late-onset mammary carcinoma development. Preliminary results from an outcross to C57BL/6J mice indicated that the genetic background (C3B6F1) significantly influences disease course and severity. By longitudinal in-vivo monitoring of disease progression on different genetic backgrounds we aim to identify relevant unknown genetic modifying factors. Here we report on the clinical and pathological characterization of this novel disease model on C3H and C3B6F1 background.


References: Lennartsson and Rönnstrand (2012): Stem Cell Factor/ c-Kit: From basic science to clinical implications. Physiol Rev 92: 1619-1649

Hrabe de Angelis et al. (2000): Genome-wide, large-scale production by ENU mutagenesis. Nature Genet. 25(4): 444-447

Aigner, Rathkolb et al. (2011): Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in hematological parameters. Mamm Genome 22: 495-505

Birgit Rathkolb

Helmholtz Center Munich, German Mouse Clinic (GMC), Germany

10:45 - 11:15Coffee Break 
11:15 - 11:35
From the Bytes to the Bedside: The Role of Collagen XVIII in Normal and Malignant Hematopoiesis

Lakkala, Juho a, Kaur, Inderjeeta a, Devarajan, Raman a, Savolainen, Eeva-Riitta b, Heljasvaara, Ritvaa a, Pihlajaniemi, Tainaa a, Izzi, Valerio a,c


a Faculty of Biochemistry and Molecular Medicine, University of Oulu, Finland

b Dept. of Hematology, Oulu University Hospital, Oulu, Finland

c The Finnish Cancer Institute, Helsinki, Finland


The endless combinations of extracellular matrix (ECM) proteins, cytokines, chemokines and growth factors – collectively known as the matrisome – present in the tumor microenvironment play a paramount role in all stages of tumorigenesis. This is also true for acute myeloid leukemia (AML), though in the case of liquid neoplasms the ECM is mostly believed to be produced and modulated by stromal cells.

In our work, we have made use of big data to identify ECM moieties associated with AML progression and chemoresistance and identified Collagen XVIII (Col18a1) as an important gene for disease progression. Generation of mouse lines defective for Col18a1 confirmed these findings, demonstrating that the lack of this collagen triggers a transplantable, CD47-dependent cell-intrinsic myeloproliferative state that aggravates over time and configures as a form of pre-leukemia, which can be reverted by specific recombinant moieties of Col18a1.

These findings open new prognostic possibilities for the management of AML progression and suggest novel molecular interactions worth further exploration for the development of novel therapeutic approaches.


Valerio Izzi

University Oulu, Faculty of Biochemistry and Molecular Medicine, Finland

11:35 - 11:55
Predictive modeling, applied to genetically engineered mouse models of breast or lung cancer, provides insights into major oncogenic pathways

The CanPathPro Consortium


Banga, Julio1, Frappart, Lucien2, Hasenauer, Jan3, Herault, Yann4, Jonkers, Jos5, Koubi, David6 , Lange, Bodo7, Lines, Glenn8, Ploubidou, Aspasia2, Rinner, Oliver9

1 Spanish National Research Council, CSIC, Spain

2 Leibniz Institute on Aging, Germany

3 Helmholtz Zentrum München GmbH, Germany

4 Institut Clinique de la Souris, France

5 Netherlands Cancer Institute, The Netherlands

6 Finovatis SAS, France

7 Alacris Theranostics GmbH, Germany

8 Simula Research Laboratory AS, Norway

9 Biognosys AG, Switzerland


The H2020 project CanPathPro is building and validating a computational predictive modelling platform applied to cancer. To this end, we develop and refine bioinformatic and experimental tools, utilized in generation and evaluation of systems biology modelling predictions.

The presented work employs following technologies and methodologies:

  • biological systems representing 3 levels of biological complexity (genetically engineered mouse models –GEMMs– of breast or lung  cancer, organoids and cell lines derived thereof);                                                                                                                    
  • next generation sequencing and SWATH-based phospho/proteomics;                                                                                      
  • two large-scale computational mechanistic models.


The highly-defined biological systems are used (i) to activate selected oncogenic stimuli that modulate pathway components in a systematic manner; (ii) to characterize the signaling changes occurring during cancer development - thus generating temporally resolved datasets for model training; and (iii) to validate, in vitro and in vivo, the modelling predictions.


The mechanistic models, based on ordinary differential equations, enable prediction of phenotypes and drug response in mouse or human. Model parameters are defined using project-derived experimental data, either via parameter estimation strategies or via selection of parameter distributions by a Monte Carlo approach.


In conclusion this work encompasses a highly integrative systems biology approach generating and validating new hypotheses on cancer pathways signaling and cross-talk identifying new signal flow and suggests new ways to interfere with tumor growth.

Bodo Lange 

Alacris Theranostics, Germany

11:55 - 12:05Twitter Poster Session



SESSION 3 - European Cancer Research Policy

Chair: Michael Raess, INFRAFRONTIER GmbH, Germany

13:00 - 13:30
Keynote: Cancer: a growing challenge for Europe

Tomi P. Mäkelä

University of Helsinki & Mission Board for Cancer

Europe has only 10% of the world’s population, and yet 25% of cancer cases - and this grand challenge is rapidly getting worse due to the aging population. On the other hand Europe has a unique opportunity to provide global solutions to this challenge with the possibility for large data an sharing in a way ensuring privacy and maintaining citizen’s trust. The recent proposal for #MissionCancer (1) leverages these opportunities in recommendations to start a new European initiative to understand, to implement prevention programs, to develop diagnostics and treatments, and to engage patients and citizens e.g. through a European patient-driven digital center. The ambitious and tangible goal is to save three million lives by 2030 and to improve the quality of life of the increasing numbers of survivors. Regarding the subject of this conference the initiative is very pertinent as it aims to obtain a comprehensive and dynamic view of the development and spread of cancer in the context of the host for improved prevention, diagnosis and treatments. The potential for increasing our understanding in this area is demonstrated by the significant benefit obtained through targeted therapies and host immune activation against some tumours. Recent technological developments and European collaborations provide an excellent opportunity for realising this potential but this requires a new level of investment in innovative research utilising relevant research infrastructure and investing in the development of new models and technologies interrogating the interactions of cancers and their host. Animal models are of course a cornerstone in cancer models and hold immense potential especially in comparative studies with patient material. is proposed to be established with the collaboration of relevant stakeholders, and here Infrafrontier as a European level infrastructure in a key area is very important.

1. CONQUERING CANCER: MISSION POSSIBLE. Report of the Mission Board for Cancer

Tomi Mäkelä

Helsinki Insitute of Life Science (HiLIFE), Finland

Member of EU Cancer Mission Board

13:30 - 13:45

INFRAFRONTIER - Rodent models for understanding cancer

It is the mission of INFRAFRONTIER to provide unique scientific resources, services, and expertise to advance the understanding and treatment of human diseases using rodent models (mice and rats). Biomedical researchers worldwide gain access to precision model development, systemic phenotyping, and to more than 7600 mouse strains archived in the European Mouse Mutant Archive (EMMA).

To enhance our understanding of cancer, INFRAFRONTIER offers specialised resources such as a unique archive of embryonic stem cells derived from validated genetically engineered mouse models of cancer provided by the Netherlands Cancer Institute as, well as curated cancer mouse models that are available to the cancer research community. The recently published INFRAFRONTIER Cancer Resource allows to browse the entire EMMA collection for genetic associations with 50 different cancer types. The INFRAFRONTIER mouse clinics provide access to specialised platforms to study the interaction of phenotype expression with specific environmental factors, such as diet, air pollution, exercise, or stress and thereby determine risk factors for cancer onset and progression, allowing conclusions for its prevention, diagnosis, and treatment.

Together with the other Life Science Research Infrastructures INFRAFRONTIER is prepared to make the Horizon Cancer Mission a Mission Possible.


Michael Räß


13:45 - 14:00
EurOPDX/EDIReX, a Research Infrastructure that provides access to standardized PDX resources and data in Europe and globally

Massimiliano Borsani1, Emilie Vinolo2

Cancer cell lines used to be the gold standard in preclinical studies, but they show a high failure rate in predicting therapeutic responses in patients. Patient-derived cells and tumours are gaining more attention in cancer modeling, necessary for precision medicine approaches. In particular, Patients-Derived tumour Xenografts (PDXs) are emerging as a promising tool to address clinically relevant questions [1].

Launched in 2013, the EurOPDX Consortium gathers 18 research institutions (, with the goal to maximize exploitation of patient-derived models by: (i) integrating institutional collections into a single virtual repository; (ii) defining common standards, thus improving preclinical data reproducibility (FAIR principles, [2]); (iii) sharing models within and outside the consortium to perform collaborative precision oncology “xenopatient” trials.

EurOPDX is now running a 4-year project (EDIReX project, H2020 grant no. 731105) to build a specific distributed Research Infrastructure (RI) to offer access to PDX resources through Trans-National Access calls and web portals, like the new EurOPDX Data Portal ( for model selection and data browsing, and a dedicated instance of the cBioPortal ( for model-associated molecular data.

Aims and advantages of a RI for patient-derived models will be discussed.



[1] Byrne, A., Alférez, D., Amant, F. et al. Nat Rev Cancer 17, 254–268 (2017).




1 European Institute of Oncology, Milano, Italy.

2 Seeding science SRL, 1342 Limelette, Belgium.

Massimiliano Borsani

EurOPDX, Italy

14:00- 14:15

Euro-Bioimaging - Spanning the bridge from the bench to the bedside

John Eriksson

Euro-BioImaging (EuBi), Finland

14:15 - 14:30
Mission Impossible? Instruct-ERIC: structural biology tackling cancer

Instruct-ERIC, Instruct Hub, Oxford, UK

European Research Infrastructures have the ability and capacity to deliver scientific breakthroughs and to foster innovation. Instruct is well placed to contribute to Mission Areas by making the existing structural biology community available to contribute to a scientific programme and also to engage with the wider research community which needs structural biology techniques to integrate with their existing research effort. Structural biology can provide key data to help understand the molecular processes involved in cancer and the host interactions, both of which are crucial for diagnosis and development of treatments for cancer. More specifically, structural biology is not only structure determination, but is increasingly developing methods to identify dynamic functionality in the cell in real time. It can provide insights for the design and efficiency of novel cancer therapies including the identification of drug candidates and to understand their function in the cellular context. Similarly, it can identify drug resistance mechanisms and help to engineer personalised drugs for individual cancer targets. Advanced AI techniques, such as structure-based virtual screening, are now available for predicting potential functional ligands. Instruct already supports cancer research through its access programme: 30% of access proposals received in the last year were related to cancer and the talk will briefly present some examples of research undertaken by Instruct Centres in this area. 

Susan Daenke

Instruct - ERIC, UK

14:30 - 14:45
EU-OPENSCREEN, the European Research Infrastructure for Chemical Biology and early Drug Discovery

Chemical compounds, which are selected for their ability to exert a specific biological effect on cellular targets, represent versatile tools in basic research to advance our understanding of pathologies at the molecular and cellular level and to validate novel drug targets. At the same time, bioactive compounds can be translated into novel drug candidates as promising starting points for the development of new effective cancer treatments. In fact, the majority of marketed drugs today are small chemical molecules.

These chemical compounds are indispensable tools for the development of novel therapies, but their identification requires significant efforts in terms of state-of-the-art facilities, expertise (e.g. in assay development or medicinal chemistry) and resources (e.g. comprehensive compound collections), which are unavailable to the majority of academic researchers.

As the European Research Infrastructure for Chemical Biology and early Drug Discovery, the EU-OPENSCREEN ERIC ( accelerates drug discovery efforts in an open-access setting with researchers from academia and industry. All generated tool compounds and associated bioactivity data are made available to the global scientific community.


[1] Brennecke, P. et al., SLAS Discov. 2019 Mar;24(3):398-413. doi: 10.1177/2472555218816276

[2] Stechmann, B., Fecke, W., IntechOpen. doi: 10.5772/intechopen.91138

Authors 1 EU-OPENSCREEN ERIC, Berlin, Germany

Bahne Stechmann


14:45 - 15:00
The research we want- a researcher turned patient advocate on research that matters to patients

After losing her husband to Melanoma, BR founded a European patient network, the Melanoma Patient Network Europe. With a medical degree and a PhD in Biomedical Sciences, her interest has been in patient-centric research and today, the network is involved in numerous research initiatives. In this talk, BR will reflect on the unique perspective on research that patients can provide- and how to leverage its benefits. 




Bettina Ryll

Melanoma Patient Network Europe (MPNE)

Member of EU Cancer Mission Board

15:00- 15:45

Panel Discussion: How can European Life Science Research Infrastructures contribute to the Cancer Mission?

Tomi Mäkelä 

Michael Räß 

Massimiliano Borsani 

John Erikkson

Susan Daenke

Bahne Stechmann

Bettina Ryll

15:45 - 16:00

Wrap up



Registration is now closed. 

Twitter Poster Session

The Online Twitter Poster Session will take place from Oct 7 noon to Oct 8 noon on Twitter. Please tweet your posters at a time most convenient to you, depending on your time zone. All official virtual posters will be retweeted from @InfrafrontierEU. Selected posters will be showcased in Session 2 on Oct 8. Here are the guidelines. Please use this template to make your poster. 

What is an Twitter poster session?

Instead of a conventional poster session wherein the printed poster is displayed, and the author present these posters to an audience at the conference venue, this online poster session will take place on Twitter. The participants will tweet their posters in the form of images accompanied by a brief summary. Please include your contact information (email address, etc.) on the poster slides for further interaction with interested viewers. 

Find the instructional video here.

Please contact Asrar Ali Khan and Spela Kosir ( if you have any questions.  


Here is how INFRAFRONTIER supports Cancer Research