Project Details
Description
Aim: the overall goal is to tailor cancer treatment by genetic profiling of patients, reducing the risk of relapse
and serious toxic side effects.
Background: cancer is a leading cause of death in humans (13% worldwide). Furthermore, cancer patients
differ widely (but unpredictably) in the efficacy of chemotherapy and toxicities they experience. This variation
in treatment response can to a certain degree be explained by genetic variation between patients. Thus, there
is a need to explore the genetic diversity of patients in order to improve both drug dosage and identify patients
at increased risk of specific toxicities.
Significance for childhood cancer: using childhood acute lymphoblastic leukemia (ALL) as a model cancer and
applying innovative approaches within bioinformatics and systems biology, we will address the major obstacles
hitherto faced when exploring the associations between host genomic variants and response to chemotherapy.
The results obtained will be part of near-future randomized clinical trials in childhood leukemia, investigating
personalizing chemotherapy.
Preliminary results, workplan and methods: the present study will perform targeted, but extensive and precise
genome-wide profiling of clinical relevant single nucleotide polymorphisms (SNPs). Clinical relevant genes and
SNPs within ALL therapy have been mapped and 35.000 SNPs selected. This panel will now be updated in order
to fully cover clinical relevant SNPs within areas as drug disposition, immune function and several organ
toxicities. Furthermore, we wish to improve our in-house targeted multiplexed sequencing platform for
genotyping, enabling us to cover more of the targeted genome, perform a higher multiplexing and deeper
sequencing. Finally, we will investigate ALL patients’ genetic profiles in relation to 1) the 20 most common
serious treatment-related toxicities, 2) early treatment response measured at 3 time points during treatment
and 3) risk of relapse.
and serious toxic side effects.
Background: cancer is a leading cause of death in humans (13% worldwide). Furthermore, cancer patients
differ widely (but unpredictably) in the efficacy of chemotherapy and toxicities they experience. This variation
in treatment response can to a certain degree be explained by genetic variation between patients. Thus, there
is a need to explore the genetic diversity of patients in order to improve both drug dosage and identify patients
at increased risk of specific toxicities.
Significance for childhood cancer: using childhood acute lymphoblastic leukemia (ALL) as a model cancer and
applying innovative approaches within bioinformatics and systems biology, we will address the major obstacles
hitherto faced when exploring the associations between host genomic variants and response to chemotherapy.
The results obtained will be part of near-future randomized clinical trials in childhood leukemia, investigating
personalizing chemotherapy.
Preliminary results, workplan and methods: the present study will perform targeted, but extensive and precise
genome-wide profiling of clinical relevant single nucleotide polymorphisms (SNPs). Clinical relevant genes and
SNPs within ALL therapy have been mapped and 35.000 SNPs selected. This panel will now be updated in order
to fully cover clinical relevant SNPs within areas as drug disposition, immune function and several organ
toxicities. Furthermore, we wish to improve our in-house targeted multiplexed sequencing platform for
genotyping, enabling us to cover more of the targeted genome, perform a higher multiplexing and deeper
sequencing. Finally, we will investigate ALL patients’ genetic profiles in relation to 1) the 20 most common
serious treatment-related toxicities, 2) early treatment response measured at 3 time points during treatment
and 3) risk of relapse.
| Status | Finished |
|---|---|
| Effective start/end date | 01/01/2014 → 31/12/2018 |
Collaborative partners
- Technical University of Denmark (lead)
- University of Gothenburg (Project partner)
- The National University Hospital of Iceland (Project partner)
- Rigshospitalet (Project partner)
- University Hospital Herlev (Project partner)
- Helsinki University Central Hospital (Project partner)
- Vilnius University Children Hospital (Project partner)
- Oslo University Hospital (Project partner)
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