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Grants in cancer research

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Laureates 2024 - 2025

Emily ALOUANI
Camille EVRARD
Léa DOUSSET
Mihael ALDEA
Nikolaus DEIGENDESCH
Romain LEVY
Lauriane LEMELLE

Emily ALOUANI

Title of the project: Impact of aneuploidy level on immune escape and resistance to immunotherapy in colorectal cancer (CCR)

Current location: CHU de Toulouse, 1 avenue du Pr Poulhès 31059 Toulouse Cedex 09

Fellowship location: Memorial Sloan Kettering Cancer Center, 1275 York Avenue New York 10065

Summary of the project: Chromosomal instability is a type of genomic instability where entire chromosomes or their segments are duplicated or deleted resulting in numerical and structural chromosomal complexity (aneuploidy). Various studies showed that tumors with high aneuploidy escape immune surveillance and impart resistance to drugs notably immune checkpoint inhibitors (ICI). While former studies focused on models with established high aneuploidy, an unanswered question is how varying levels of aneuploidy influences this phenomenon. Our hypothesis is that the level of aneuploidy and its intrinsic mechanism has an impact on immune escape and resistance to ICI. We will therefore characterize aneuploidy level in different MMRp (MisMatch proficient) and MMRd (deficient) CRC in patients and study the association between aneuploidy level and response to ICB. We will then generate well defined pMMR and dMMR murine cancer models with different levels of aneuploidy to study further the impact on immune escape. We will monitor outcomes over time either in the absence or in the presence of ICI. Identifying the mechanisms by which aneuploidy leads to immunosuppression would pave the way for the development of innovative therapeutic strategies for most immunoresistant tumors.

Camille EVRARD

Title of the project: Test of novel treatment compounds in cancer/stroma heterospheroids to identify metabolic vulnerabilities in pancreatic ductal adenocarcinoma

Current place of work: Poitiers University Hospital, Medical Oncology Department

Place of training: Karolinska Institut, Stockholm, Pancreatic cancer research laboratory

Summary of the project: Pancreatic cancer is a cancer for which the number of new cases has been increasing rapidly in recent years. Moreover, this type of cancer has a very poor prognosis and the innovative therapies of recent years have been ineffective against it.

There is therefore an urgent need for a better understanding of the multiple mechanisms of resistance in pancreatic cancer to improve its prognosis.

Several studies carried out in the host laboratory (Karolinska Institute, Stockholm) have shown that 3D cell culture models ('heterospheroids') reflect pancreatic cancer more realistically than 2D cell cultures.

To identify promising new therapies for this type of cancer, I will be testing new molecules on these 3D cell culture models of pancreatic cancer.

Léa DOUSSET

Title of the project: Genomic insights and personalized therapy for advanced cutaneous squamous cell carcinoma in solid organ transplant recipients.

Current fellowship location: Experimental Dermatology Group, Pr Kiarash Khosrotehrani
Frazer Institute, The University of Queensland, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Australia.

Current affiliation: Dermatology department, pr Beylot-Barry, Bordeaux University Hospital, France
Inserm U1312-BoRdeaux Institute of onCology (BRIC), Team 5 "Translational Research on Oncodermatology and Orphean skin diseases (TRIO2)", Dr Hamid Rezvani/Pr Marie Beylot- Barry, Bordeaux University, France.

Summary of the project: Solid organ transplant recipients (SOTRs) have a high risk of aggressive skin cancers, notably cutaneous squamous cell carcinoma (cSCC), with a 165-fold increase in incidence. Current treatments for advanced cSCC in SOTRs are limited and often ineffective, prompting the need for new solutions. Surgical or radiological interventions are not feasible, leaving palliative care or immune checkpoint inhibitors as options, despite the risk of organ rejection. Lack of predictive markers and understanding of cSCC genetics hinder treatment success. Our project aims to employ long-read DNA sequencing to understand the genomic alterations of advanced cSCC in SOTRs, paving the way for precision medicine. Eligible patients for this phase II, open-label, single-center study will then receive cetuximab, an anti-EGFR antibody, in combination with prochlorperazine, an endocytosis inhibitor, to inhibit cancer cell evasion mechanisms. Expected outcomes include the identification of predictive biomarkers and therapeutic targets specific to cSCC in organ transplant patients, as well as assessment of clinical response. This integrated approach could significantly improve disease management and address a critical medical need.

Mihael ALDEA

Title of the project: MYC-amplified non-small cell lung cancer: Genomic, phenotypic features and impact on survival outcomes

Current place of work: Dana-Farber Cancer Institute, Boston, USA

Place of usual professional activities: Gustave Roussy, Villejuif, France

Summary of the project: This study addresses the role of MYC amplifications found in over 10% of non-small cell lung cancer (NSCLC) cases, suspected of contributing to therapeutic resistance. By exploring the genomic and immune landscape of these cancers, our goal is to uncover effective drug combinations to enhance treatment efficacy. We plan to analyze over 6000 advanced NSCLC patients, including around 400 with MYC amplification, using the high-precision, multiplexed immunofluorescence imaging of the Orion platform. This project aims to identify novel predictive biomarkers and unveil specific vulnerabilities, paving the way for optimizing therapies.

Nikolaus DEIGENDESCH

Title of the project: Spatial tissue proteomics of non-small cell lung cancer (NSCLC)

Current location: Institute of Pathology, University Hospital Basel, Switzerland

Fellowship location: Institute of Innate Immunity, Department of Systems Immunology and Proteomics, University of Bonn, Germany

Summary of the project: Worldwide, lung cancer is the most prevalent malignancy and a leading cause of cancer deaths, with non-small cell lung cancer (NSCLC) being the most common type. Despite significant advancements in identifying genetic alterations in NSCLC, many patients still lack suitable therapeutic targets, and the reasons for poor treatment response remain unclear. Next-generation sequencing (NGS) approaches, though cost-effective, often fail to classify numerous genetic alterations. In contrast, proteins, regulating crucial biological functions, offer promising insights into tumor biology beyond genetic analysis.

My research project aims to investigate NSCLCs through spatial tissue proteomics, a cutting-edge technology to examine the protein landscape within tumor tissue. Using formalin-fixed paraffin-embedded (FFPE) tissue samples derived from patients to analyze different histological regions, the project seeks to uncover tumor heterogeneity and understand the tumor microenvironment's impact on disease progression and therapy response.

The accurate characterization of molecular signatures of tumors on protein level could lead to their use as future biomarkers for precision oncology, paving the way for improved patient outcomes in the future.

Romain LEVY

Title of the project: Preclinical gene-editing approaches for ataxia-telangiectasia

Current place of work: Unité d'Immunologie-Hématologie et Rhumatologie Pédiatrique (UIHR), Hôpital Universitaire Necker - Enfants Malades, 149 rue de Sèvres - 75015 Paris, France

Fellowship location: Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142
David R. Liu Lab

Summary of the project: Ataxia-Telangiectasia (A-T), is an untreatable disease caused by mutations in ATM gene, and can affect 1 in 40,000 births. A-T manifests as early onset neurological decline, profound immunodeficiency, and cancer. Patients have an average life expectancy of 25 years, a figure that has not changed since the 1950s. A recent set of precision gene-editing technologies have the potential to introduce genetic corrections of different sizes, while preserving the regulation of the gene expression. We hypothesize that ATM functionality can be rescued in vivo, with our goal to develop preclinical precision gene editing strategies and delivery methods for potentially curing A-T, a major unmet medical need.

Lauriane LEMELLE

Title of the project: Investigating the role of Hippo/YAP1 pathway during neuroblastoma’s metabolic reprogramming

Current place of work: Pediatric Oncology Center SIREDO, Institut Curie, 26 rue d’Ulm 75005 Paris.

Fellowship location: Pr Franco Locatelli lab, supervisor Dr Angela Di Giannatale, Ospedale Pediatrico Bambino Gesu, Roma

Summary of the project: Neuroblastoma (NB) is the most commonly extra-cranial solid tumor in children. Despite intensive multimodal therapy, patients with high-risk and relapsed NB face a poor prognosis. Therefore, the understanding of mechanisms involved in aggressiveness and dissemination is fundamental in order to develop new therapeutic approaches. YAP1, a downstream effector of the Hippo pathway, has been reported to be a prognostic factor in many tumors, including pediatric cancers such as NB. Indeed, it has been demonstrated that YAP1 contributes to cell identity, tumor initiation, metastasis, angiogenesis, and resistance to chemotherapy. Specifically, YAP1 transcription activity has been showed to be increased in high-risk and relapsed NB suggesting its potential role in tumor’s aggressiveness. Among its different functions, YAP1 is involved in glucose metabolism both in normal and cancerous cells. Recent researches have shown that YAP1 is able to regulate the expression of glucose transporter of the GLUT family. The role of YAP1 in metabolic activity is little known in NB and thus a deeper study of this aspect could lead to the identification of therapeutic targets. In this work I will investigate the expression of YAP1 and GLUT transporters in NB cell lines and tissues and explore the down-stream interactors of YAP1, which are involved in metabolism. I will study the role of YAP1 in NB metabolism and if YAP1 could modulate exosomes release and content. Lastly, I will explore the potential prognostic value of circulating exosomes as metabolic related disease biomarkers in NB patients.