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The potential of liquid biopsies in cancer research2016
2 © GATC Biotech 2016
Tumors shed both intact cells (resulting in circulating tumor cells) as well as cellular components, such as nucleic acids (resulting in cell-free DNA or RNA).
Liquid biopsy: circulating biomarkers for cancer
Diaz, Jr., L.A. and Bardelli, A. (2014) “Liquid biopsies: genotyping circulating tumor DNA.” Am. Soc. Clin. Oncol. 32, 579.
3 © GATC Biotech 2016
Circulating cell-free DNA can be found under physiological as well as pathophysiological conditionsderives from necrotic and apoptotic tissue/cells is highly fragmentedctDNA is only a minor fraction of cfDNA
Origin of circulating cell-free DNA
Crowley et al., 2013
4 © GATC Biotech 2016
Applications for liquid biopsy
Non-invasive prenatal diagnosticsChromosomal aberrationsSub-chromosomal aberrations
Pathogen detectionVirusBacteria
Detection of rejection after transplantation
Cancer diagnostics Early detectionTreatment selectionTherapy monitoring
5 © GATC Biotech 2016
Early detection of cancer is crucial!
Tumour growth and metastasis
Source: American Cancer Society
stage 5-year survival CRC 5-year survival breast cancer
0 100% 100%I 92% 100%II 63-89% 93%III 53-89% 72%IV 11% 22%
6 © GATC Biotech 2016
Limitations of tissue biopsy
Biopsy is invasiveMay not be feasible based on patient condition or tumour accessibilityImpractical for periodic monitoring for progression recurrence
Cancer is a heterogeneous diseaseMolecular properties differ within tumoursPrimary tumour biopsy may not reflect current disease condition (clonal evolution)
Surgery is costlyGreater demand due to molecular profiling
7 © GATC Biotech 2016
Liquid biopsy for cancer detection
Bettegowda et al 2014.
The opportunityCirculating tumour DNA (ctDNA) is easy accessible and can be detected in most metastatic cancers
The challengectDNA is often only present at low levels
8 © GATC Biotech 2016
cfDNA is highly fragmentedDNA content differs largely (1-100 ng / mL plasma)
Characteristics of cell-free DNA
9 © GATC Biotech 2016
Challenges of ctDNA
Crowley et al., 2013
How to discriminate between ctDNA and ‘normal’ cfDNA?
10 © GATC Biotech 2016
Alterations of ctDNA
Crowley et al., 2013
Point mutationsInsertions / DeletionsCopy number variationsStructural changes or rearrangements (gene fusions)Hypo- and/or hypermethylation
11 © GATC Biotech 2016
Challenges of ctDNA
Crowley et al., 2013
How to discriminate between ctDNA and ‘normal’ cfDNA?
How to detect very low levels of ctDNA?
How to quantify the number of mutant DNAs in a sample?
12 © GATC Biotech 2016
- services for cancer research
Unbiased discoveryExome sequencing of matched samples from tumour tissue, cell-free DNA and blood
ONCOEXOME
Targeted screeningPanel sequencing of clinically actionable mutations, including low frequency mutations
ONCOPANEL
MonitoringFrequent detection of single driver mutations after treatment, such as surgery or therapy
ONCOTARGET
13 © GATC Biotech 2016
- services placed on the cancer treatment timeline
Screening Diagnosis Follow-upTreatment
STAGING SURGERY | CHEMO | RADIATION RECUPERATIONBiopsyImagingTumour sizeMolecular stratification
Tumour removalIrradianceMedication
Monitoring
Diagnosis
Adjuvant treatment decisionCompanion diagnosticsMeasurement of therapeutic response Follow-up
ONCOEXOMEONCOPANEL
ONCOTARGET
14 © GATC Biotech 2016
Thank you very much for your attention