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Project

Genomic analyses of liquid biopsies for diagnosis, monitoring and therapeutic stratification of paediatric cancers.

While global survival of paediatric cancer is reaching up to 80%, cure rates remain disappointingly low for certain high risk types of tumours and for most relapsed cases. Moreover, studies on late effects of cancer treatment are showing high rates of chronic disease due to treatment related toxicities indicating the need for less toxic treatments in children.

Recent advances in genomic profiling techniques have enabled the study of cancer genomes with unprecedented detail and offer novel opportunities for precision medicine guided treatment. However, classical tumour biopsy sampling is invasive and consequently painful and even risky for the patient. Moreover, commonly used small (tru cut) biopsies only reflect a spatially limited snap-shot of the heterogeneous genomic landscape of the primary tumour. For metastatic lesions, generating a comprehensive cancer genome profile is even more challenging with traditional biopsy methods. As a consequence, actionable therapy resistance driving small subclones are overlooked thus seriously impeding the presumed power of current targeted therapy protocols.

Recently, genome wide sequencing methods have emerged, allowing powerful and sensitive genomic analysis of free circulating tumour DNA (ctDNA) in noninvasive liquid biopsies. These noninvasive techniques hold the promise of rapid, safe and highly informative genetic analysis, even potentially identifying small tumours not yet visible by currently used imaging techniques. Although promising, liquid biopsies require further exploration regarding specificity, sensitivity and informative power at diagnosis as well as for prognosis and for monitoring therapy response and early detection of relapse.

In this project, we will perform an in depth exploration of the potential of liquid biopsies in the genetic work up, follow up and clinical management of neuroblastoma patients. We will apply our novel analytical pipelines for shallow whole genome DNA copy number analysis, whole exome sequencing, deep targeted sequencing and digital droplet PCR to compare diagnostic and relapse patient blood samples (ctDNA) with data from tumour biopsies and disseminated tumour cells (DTCs) to improve diagnosis, risk stratification and patient follow-up and to generate a more complete picture of tumour heterogeneity, in particular for therapeutically actionable subclones. In addition, we will also evaluate the feasibility of using liquid biopsy sampling for measuring therapy response and detecting early relapse. Finally, we will also initiate a proof-of-principle study for liquid biopsies in patients with other paediatric solid tumours.

Date:1 Nov 2018 →  31 Oct 2023
Keywords:paediatric cancers
Disciplines:Other paramedical sciences, Palliative care and end-of-life care, Regenerative medicine, Other health sciences, Laboratory medicine, Other clinical sciences, Other basic sciences, Other translational sciences, Other medical and health sciences, Nursing