Cancer represents a formidable current and future global health challenge. The LUMC Medical Research Profile Cancer Pathogenesis and Therapy has the mission to meet this challenge by developing and implementing innovative patient-tailored, multimodal diagnostic methods and treatment modalities. Our multidisciplinary approach aims to integrate and translate excellent results of basic research in cancer genetics, molecular cell biology, and immunology into precision cancer care. Besides common cancer types, the translational research efforts focus in particular on selected tumour types for which the LUMC represents a national and international referral center.
Focus on three major themes
Cancer Genetics and Epigenetics
The research in this theme focuses on
- heritable DNA variation and its association with cancer predisposition (leading to familial cancer syndromes) and response to therapy (i.e. pharmacogenetics);
- somatic genetic changes occurring during tumour development that strongly determine tumour biology and clinical behaviour.
Advances in DNA/RNA sequencing technology are impacting both areas, improvingdiagnostic classification of tumours and risk estimates for hereditary cancer syndromes. Research aimed at integrating full genome analysis, transcriptomics, epigenomics, and protein biomarkers will further enhance the individualisation of cancer care at the level of prevention, early detection, diagnosis and choice of treatment.
Fundamental tumour-host studies focusing on the improvement of the tumour-specific immune response will move the modality of immunotherapy forward by
- the identification of new targets;
- the alleviation of immune regulatory mechanisms;
- studies on the pharmacokinetics of immunotherapeutic modalities;
- analysing the type of therapy versus stage of disease, including treatment of metastases;
- exploring combinations of new and established therapies;
- integrating the role of genetics and age;
- incisive state-of-the-art immune monitoring.
Optimal usage of animal models, patient cohorts and clinical trial data will validate new immunotherapeutic (multi)modalities and the definition of biomarkers that can be applied for the selection of patients and the prediction of successful therapy.
This multifaceted theme integrates on target identification and validation for drug discovery and clinical testing of novel targeted therapies and drug repurposing within cell signalling pathways affecting
- cell proliferation and apoptosis;
- the efficacy of immune-, radio- and chemotherapy;
- the induction of tumour angiogenesis and metastasis.
Experimental approaches involve in-depth studies of the cellular and molecular mechanisms that cause normal cells to become tumorigenic, using appropriate in vitro and animal models. Results will stimulate the development of novel, rationally designed therapies that target previously overlooked cancer-promoting mechanisms while striving for low toxicity and favorable cost-effectiveness.
The existing LUMC technology platforms facilitate detailed characterisation of suitable model systems and patient biosamples to establish links between the genetic and proteomic profile of the patient (i.e., the host), the molecular aberrations of the tumour and its microenvironment and the clinical outcome of patient cohorts and individuals. Translation into the clinic will be facilitated by internationally acclaimed LUMC expertise in conducting investigator-initiated clinical trials. An important aspect is the integration of novel molecular and in vivo imaging technology. The essential LUMC research infrastructure that supports our goals includes:
- the Leiden Genome Technology Center (LGTC) for the development of complete and massive parallel sequencing of patient and tumour genomes, epigenomes, and transcriptomes;
- the Sequence Analysis Support Core (SACS) for genetic data analysis;
- the Center for Proteomics and Metabolomics (CPM);
- prospective and comprehensive biobanking;
- the GMP-certified Interdivisional GMP Facility Leiden (IGFL) for the production of experimental drugs for therapy and imaging purposes;
- clinical trial units linked to national and international data centers.
The individual Themes and Research groups maintain collaborations with diverse groups within the Netherlands and internationally within and outside Europe.
Dutch science agenda
The medical research profile Cancer Pathogenesis and Therapy participates in the Nationale Wetenschapsagenda (in Dutch).