Title Promoter Affiliations Abstract "Coevolution of epithelium in colorectal cancer: comprehensive characterization of progress-associated tumor heterogeneity in the colorectal cancer" "Sabine Tejpar" "Digestive Oncology" "To understand the characteristics of colorectal cancer (CRC), diverse molecular classifiers have been generated. But these only capture the characteristics of the tumor at a specific stage or in a specific section. CRC has continuously evolving entities, with a complex adenoma-carcinoma sequence and later carcinoma-metastasis sequence, in a continuous coevolutionary crosstalk with the tumor microenvironment. Our past work has shown representative features in the carcinoma, and the current work will elaborate these in detail, integrating different data inputs needed to characterize the dynamic information in these lesions. The adenoma-carcinoma stages of CRC offer a unique opportunity, if exploited well, to understand evolutionary trajectories of the epithelium, the co-evolution of the TME and the possible impact on the targetable immune states. With this project, I will characterize the tumor cells’ sub-characteristics within classified epithelial molecular groups with integration approaches of bulk, single-cell and spatial technologies. In the preliminary data, the heterogeneous pattern within molecular subtypes can clearly be found. Especially, the understudied non adenomatous lesions, non-canonical Wnt driven tumors show very interesting heterogeneity and novel cancer stem cell dynamics. Collectively, signatures combined with bulk-, single-cell RNA sequencing and spatial techniques will identify the optimal stratification for CRC prognosis and therapy." "STAND UP TO CANCER: Integration of individual cancer genes in signalisation network in pediatric tumors" "Department of Biomedical molecular biology" "geen abstract" "Cell-cell cOmmuNicaTion As a driver of Cancer cell state identiTy - Decoding the impact of cell-cell communications on the identity of tumor states in skin cancers" "Yvan Saeys" "Department of Applied Mathematics, Computer Science and Statistics, KU Leuven, Université Libre de Bruxelles, Imec" "Different tumor states (TS) exist within a given tumor with some cancer cells actively dividing, while others differentiate, invade the surrounding tissues, give rise to metastasis, or are in a dormant and therapy-resilient state. The identification of the intrinsic and extrinsic mechanisms that modulate TS diversity is essential for the development of new therapeutic strategies. In this project, we will dissect the mechanisms by which stromal-cancer cell communications influence the gene regulatory networks (GRNs), that defined TS identity in skin cancers. We will take advantage of recent advances in single-cell lineage tracing, single-cell (spatial) multi-omics, microfluidics and bio-informatics to map the spatial distribution of the different TS and their neighboring stromal cells, study how these cellular and molecular (e.g. ligand/receptor) interactions remodel the GRNs and epigenome of cancer cells and thereby regulate their specific TS identity. We will use dynamic models to assess how these interactions evolve during tumor progression, metastasis, and in response to therapy. We will reconstitute or deplete specific stromal-tumor cell interaction(s) or perturb their molecular communications and assess the impact of these perturbations on the GRN controlling TS identity. Finally, we will assess whether pharmacological interventions targeting selected stromal-tumor communications can restrict tumor growth, metastasis or alleviate resistance to therapy." "Cell-cell cOmmuNicaTion As a driver of Cancer cell state identiTy - Decoding the impact of cell-cell communications on the identity of tumor states in skin cancers" "Chris Marine" "Laboratory for Molecular Cancer Biology (VIB-KU Leuven), Laboratory of Computational Biology (VIB-KU Leuven), IMEC-Interuniversitair Micro-Electronica, Université Libre de Bruxelles, Universiteit Gent" "Different tumor states (TS) exist within a given tumor with some cancer cells actively dividing, while othersdifferentiate, invade the surrounding tissues, give rise to metastasis, or are in a dormant and therapy-resilientstate. The identification of the intrinsic and extrinsic mechanisms that modulate TS diversity is essential for thedevelopment of new therapeutic strategies. In this project, we will dissect the mechanisms by which stromalcancercell communications influence the gene regulatory networks (GRNs), that defined TS identity in skincancers. We will take advantage of recent advances in single-cell lineage tracing, single-cell (spatial) multiomics,microfluidics and bio-informatics to map the spatial distribution of the different TS and their neighboringstromal cells, study how these cellular and molecular (e.g. ligand/receptor) interactions remodel the GRNs andepigenome of cancer cells and thereby regulate their specific TS identity. We will use dynamic models toassess how these interactions evolve during tumor progression, metastasis, and in response to therapy. Wewill reconstitute or deplete specific stromal-tumor cell interaction(s) or perturb their molecular communicationsand assess the impact of these perturbations on the GRN controlling TS identity. Finally, we will assesswhether pharmacological interventions targeting selected stromal-tumor communications can restrict tumorgrowth, metastasis or alleviate resistance to therapy." "Benchmarking singlet oxygen-based photoelectrochemical detection platform for panel analysis of cancer biomarkers, using prostate cancer as a case study. A novel groundbreaking approach for cancer diagnosis and follow-up." "Karolien De Wael" "Ghent University, Antwerp Electrochemical and Analytical Sciences Lab (A-Sense Lab)" "Inspired by the EU mission regarding fighting cancer, this project commits to contribute to tackle this major societal challenge. The ""Europe's Beating Cancer Plan"", presented in 2021, has four striking targets: prevention, reduce the time to diagnosis, optimize diagnosis and treatment using personalized medicine and support the quality of life of all people exposed to cancer. This project contributes to diagnosis and follow up of the disease using prostate cancer (PCa) as a case study. More and more biomarkers are discovered and validated for cancer and the highly precise determination thereof is high on the priority list, necessitating analytical devices that allow rapid and accurate analysis with high sensitivity. Therefore, I propose the combined use of electrochemical detection with a light-triggered sensing technology for the specific and selective photoelectrochemical detection of low concentrations of three different classes of PCa biomarkers (i.e. non-coding RNA, gene fusion transcript and DNA single nucleotide polymorphism). Through the development of a 96-well plate detection platform, I will be able to perform a panel analysis of those biomarkers in 96 samples simultaneously. Detection and quantification of the selected target sequences will be performed in three different liquid biopsies (i.e. urine, plasma and serum), to ensure the translation from a lab technology to a device for hospitals." "From individual cancer genes to integrated cancer pathways in childhood cancer." "Jan Cools" "Laboratory of Molecular Biology of Leukemia (VIB-KU Leuven), Laboratory of Computational Biology (VIB-KU Leuven), Laboratory for Molecular Cancer Biology (VIB-KU Leuven), Pediatric Oncology, Department of Human Genetics, Laboratory for Genetics of Malignant Disorders" "Full exome sequencing of childhood cancers using next-generation sequencing" "Revealing the role of macrophage-associated immune-checkpoints in the sensing of apoptotic cancer cells to guide cancer chemoimmunotherapy" "Abhishek Garg" "Laboratory of Cell Stress & Immunity" "Therapeutic targeting of immune cell surface-tethered immune-checkpoints that inhibit anti-cancer immunity, via antibodies-based immune-checkpoint blockers (ICBs), has revolutionized the clinical oncological practice in recent years. Regrettably, only a subset of cancer patients tend to respond to these ICBs. Biomarker-guided, multimodal therapeutic regimen, are predicted to vastly improve the clinical efficacy of ICBs. Therein, one of the current strategies entails combinatorial application of ICBs targeting cytotoxic T-lymphocyte-associated protein (CTLA4) or, programmed cell death protein 1 (PD1)/programmed death ligand 1 (PD-L1), following cytotoxic (i.e. cell death) chemo or targeted therapies. However, currently this strategy is not entirely accounting for the potential 'skewing' effects of cancer cell death on immune-checkpoint landscape since dying cancer cells may engage, or facilitate, inhibitory immune-checkpoints on immune cells in a manner not entirely predictable. This unpredictability arises from the poorly deciphered role of immune checkpoints in interactions with dying cancer cells. Such skewing may favor novel 'alternative' immune-checkpoints - a notion supported by our patient tumor transcriptome analyses. A 'switch' to alternative immune-checkpoints can negatively affect the efficacy of ICBs targeting conventional immune-checkpoints like CTLA4, PD1/PD-L1. Thus, systematically studying this aspect is vital for designing ‘smart’ multimodal therapies wherein ICBs are “matched” to the immune-checkpoints preferentially engaged by dying cancer cells. Hence, this project aims to decipher the cross talk between therapy-induced cancer cell death and immune-checkpoints; and study its immunological implications, to create an effective combinatorial immunotherapy regimen." "Chair Fight against Cancer for Dr. Tine Vervoort:. Psychological dimensions of pain in the context of childhood cancer." "Geert Crombez" "Department of Experimental clinical and health psychology" "In summary, the purpose of this chair (on the basis of a series of lectures at the Flemish Universities) 1) disseminating scientific knowledge about pain in children with pain is sketched from a biopsychosocial framework; 2) demonstrate the importance of pain research in the context of cancer (pediatric context) with particular attention will be paid to the importance of social context (eg, role of parents, doctors, nurses).; 3) a discussion of recent research regarding this topic and 4) a discussion of future research plans in which a) the role of emotion regulation in caretakers at the sight of pain in children (eg in the context of childhood) and their influence will systematically helping behavior be investigated and b) will be studied systematically what is the impact of childhood cancer on all family members (mothers and fathers and siblings) including family functioning and torque performance and the factors that moderate this effect (protective and risk factors). It is expected that this chair not only disseminating knowledge entails, but both clinical and academic field encourages innovative psychosocial research in the context of childhood with current and future empirical evidence will provide important tools for translation into clinical psychosocial interventions." "Understanding the role of the WNT signaling pathway in breast cancer dormancy, therapy resistance and cancer relapse." "Frederic Lluis Vinas" "Stem Cell and Developmental Biology" "Breast cancer is the most common and most deadly neoplastic disease among women worldwide. Triple-negative breast cancer is a subtype of breast cancer characterized by the lack of expression of hormone and growth factor receptors, highly aggressive clinical features, poor prognosis, and high relapse rates. The lack of hormone and growth factor receptors renders targeted therapies that are highly efficient in other breast cancer subtypes virtually useless in triple-negative breast neoplasms. Thus, chemotherapy remains the primary treatment option for triple-negative breast cancer patients.Triple-negative breast cancer patients achieve higher pathological complete response rates to neoadjuvant chemotherapy more frequently than non-triple-negative patients. However, despite the better response rates, triple-negative breast tumors still present with paradoxically higher relapse rates.The relapsing disease is a consequence of treatment failure and drug resistance. Drug resistance can be either intrinsic or acquired. Intrinsic resistance presupposes the existence of resistance-mediating features in cancer cell populations prior to treatment, ultimately causing insufficient treatment response. On the other hand, acquired resistance entails the adaptation of cancer cell populations to cytotoxic stimuli during treatment, ultimately acquiring new features that enable their survival.In recent years, several studies have confirmed that triple-negative breast cancers adapt to treatment not by selecting pre-existing resistance-mediating genotypes but rather by transitioning between different cell states and transient transcriptional and epigenetic reprogramming. However, we still lack actionable targets to prevent chemo-adaptation and acquisition of resistance and disrupt established acquired chemotherapy-resistant states.In this thesis, we sought to investigate which signaling pathways maintain stable acquired chemotherapy resistance in triple-negative breast cancers using in vitro and in vivo models of carboplatin resistance. Finally, we discovered that the primordial developmental Wnt signaling pathway maintained a stem-cell-like state in carboplatin-resistant isogenic cell lines and that disruption of Wnt ligand secretion reverted carboplatin resistance both in vitro and in vivo.We then wanted to understand which signaling pathways are modulated during acute exposure to chemotherapy. Analysis of transcriptomic datasets of breast cancer patients' paired pre- and post- chemotherapy biopsies revealed enrichment of Wnt signaling after chemotherapy treatment. Transcriptomic analysis of triple-negative breast cancer cell lines exposed to chemotherapy demonstrated early Wnt signaling enrichment upon chemotherapy in vitro. Furthermore, we determined that enriched Wnt signaling activity was a consequence of de novo transcriptional activation of the pathway in cells with inactive Wnt signaling prior to treatment. Interestingly,chemotherapy-induced Wnt-active cells appear to be more resilient and less likely to induce apoptosis while maintaining higher expression of stem cell markers and in vitro tumorsphere formation capacity. Significantly, inhibition of Wnt ligand secretion disrupts chemotherapy-induced Wnt activation and sensitizes triple-negative breast cancer cell lines to treatment.Altogether these results indicate that Wnt signaling activity contributes to stable acquired chemotherapy resistance in triple-negative breast cancers. Importantly, modulation of Wnt signaling seems to occur in the very early stages of exposure to chemotherapy. It is thus likely that chemo-adaptation and acquisition of resistance are facilitated by upregulation of Wnt signaling. Inhibiting this pathway both disarms established acquired resistance and enhances early response to treatment in vitro, suggesting this could be a potentially beneficial therapeutic strategy to enhance chemotherapeutic efficiency and prevent acquired resistance." "Screening and early detection of colorectal cancer and breast cancer in liquid biopsies using a newly-developed multi-regional methylation assay." "Guy Van Camp" "Medical Genetics (MEDGEN), Center for Oncological Research (CORE), Social Epidemiology & Health Policy (SEHPO), Radboud Universitary Medical Centre, Human molecular genetics" "Colorectal cancer (CRC) and breast cancer are amongst the most common and deadliest cancers worldwide. Early detection through current screening programs for both cancers have reduced mortality, but important limitations of these methods, such as limited sensitivity, limited specificity and invasiveness, remain. There is a need for a new, minimally-invasive, cost-effective and very sensitive diagnostic test for screening and early cancer detection. Methylated circulating tumor DNA (metctDNA) biomarkers have shown great potential to discriminate between normal tissue and tumors. MetctDNA can be detected in a minimally-invasive manner using liquid biopsies, such as plasma. Currently, DNA methylation is studied using bisulfite conversion followed by next-generation sequencing or droplet digital PCR. However, disadvantages including DNA degradation, non-optimal sensitivity and specificity of subsequent techniques and limited multiplex capacities still need to be overcome. At this moment, there exists no efficient technique for the simultaneous analysis of several methylated regions in ctDNA in one assay. In our research group, we aim to develop a new, sensitive multi-region metctDNA based bisulfite-free detection technique. The technique will be used in this project to detect differential methylation signatures between normal tissue, pre-cancerous lesions and tumors. With this approach, we aim to develop a new and better assay for screening and detection of CRC and breast cancer."