2. Introduction
Drug 1 Cured
Standard Trial and
Treatment Drug 2
error
Drug 3 Not cured
Cancer
Treatment
By predefined biomarkers
for drug sensitivity
Genetic Higher
Personalized Profiling Choose chance
Treatment Drug best drug on being
sensitivity cured
Department 2
3. Research Question
Can biomarkers be defined for
personalized anti-cancer therapy with
use of predictive modeling of drug
sensitivity?
Department 3
4. Project
Available
data types
• Panel of tumor derived cell lines corresponding to diverse
tissue types, which has been subject to extensive
NCI60 drug
molecular phenotypic and pharmacological
sensitivity
characterization
panel
• Data:
– baseline (untreated) metabolic and
transcriptional profiles from 58 cell lines
– Growth inhibition data from an array of 118
drugs
1. Cavill et al. 2009 PloS Comp
Department 4
5. Project
Available
data types
1
NCI60 drug
sensitivity
panel
Patient tumor
profiling data • Chemotherapy responses of individual cancer patients
1. Cavill et al. 2009 PloS Comp
Department 5
6. Project Methodology
• Drug-sensitivity associated
Defining pathways
Available biomarkers
data types for drug • Biomarkers: Most important
sensitivity genes or metabolites in those
1 pathways
NCI60 drug
sensitivity
panel
1. Cavill et al. 2009 PloS Comp
Department 6
7. Project Methodology
Defining
Available biomarkers
data types for drug
sensitivity
1
NCI60 drug
sensitivity
panel
Development
of predictive
models
1. Cavill et al. 2009 PloS Comp
Department 7
8. Project Methodology 1
Defining
Available biomarkers
data types for drug
sensitivity
1
NCI60 drug
sensitivity
panel
Development
of predictive
models
Patient tumor
profiling data
Testing
predictive
models
1. Cavill et al. 2009 PloS Comp
Department 8
9. Project Methodology 1
Defining
Available biomarkers
data types for drug
sensitivity
1
NCI60 drug
sensitivity
Aspired outcome
panel
Development
of predictive
models Happy
patients
Patient tumor
profiling data
Testing
Possibly
predictive
clinical use
models
1. Cavill et al. 2009 PloS Comp
Department 9
10. See you in London!
• Are there questions?
Department 10
Notas del editor
Nowadays, most cancer therapy is still a standard procedure that is similar for every patient with a type of tumor. However, this is not always beneficial because, even though the type of the tumor is similar between patients, each tumor is different on molecular level and will therefore respond differently to chemotherapeutic drugs. Another therapy would therefore be better: personalized cancer therapy. This is inidividualized therapy specifically set up for the patient. The standard procedure goes as follows: Several drugs will be tested with trial and error and the best performing drug is chosen. This can be very time consuming and can have adverse effects on the patient. Also, a patient may be cured if the right drug is found, but it can also be that none of the drug are effective, which leads to another attempt with other drugs (feedback loop). Personalized cancer therapy will begin with genetic profiling of the tumor. Because tumors are different and therefore respond differently toward certain drugs, this genetic profiling can predict which drug will work or will not work. The most effective drug can then be administered and fight the tumor. In order to predict how well a drug will perform, biomarkers for sensitivity for that specific drug or group of drugs will need to be defined that can be found using the genetic profiling.
The research question is therefore: Can biomarkers be defined for personalized anti-cancer therapy with use of predictive modeling of drug sensitivity?
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
The project will be set up as follows: Two types of data will be available: Drug sensitivity data from the NCI60 cell line panel, which is a cell line panel containing a set of 59 human cancer cell lines derived from brain, blood and bone marrow, breast, colon, kidney, lung, ovary, prostate and skin, and clinical patient data. The NCI60 data can be used to define biomarkers for specific chemotherapeutic drug. These can then be used to develop predictive models that would eventually be able to predict drug sensitivity for clinical data. When the models have been developed, the patient data can be used to test the effectiveness of the models. The aspired outcome of this project is, of course, that cancer can be treated earlier with the right drugs from the start and hopefully cure patients earlier and more effectively. Note that the defining of biomarkers already has been performed (to some extent), so the senior project will focus on the development of the predictive models.
