Patient derived xenograft models and therapy for rare or relapsed paediatric cancer
1 Formål
Cancer in children and adolescents has an overall survival rate exceeding 80%. However, each year about 40 children and adolescents die from cancer in Norway, and many of the survivors suffer from long-term effects of cancer therapy. Furthermore, cancer in children differs from cancer in adults, and there is a great need for more research focusing on paediatric cancer. This includes the establishment of animal models specifically for rare or relapsed paediatric cancers.
2 Skadevirkninger
Our planned experiments must be classified as procedures of moderate severity: implantation of human cells will be performed subcutaneously, under anaesthesia and we expect the tumour to grow up to 1 cm3.
3 Forventet nytteverdi
By developing patient specific animal models we wish to both unravel knowledge on the specific tumour behaviour, including metastasis pattern, mutational distribution and tumour progression, as well as test new drugs or drug combinations that can benefit the patient.
4 Antall dyr og art
In this study we plan to use 850 male and female NSG immunodeficient mice to develop 25 preclinical models.
5 Hvordan etterleve 3R
Central to this application ins the development of relevant models for paediatric cancers and efficacy regimes. A relevant model will provide a better recapitulation of each patients disease heterogeneity, as well as displaying the variance between patients. These mice are the only animals which will successfully engraft a manner of human cell lines and patient material, essential to development of therapeutics. The only in vitro alternative is the use of cell lines and primary patient material in culture. However , these results do not always translate into efficacy in intact biological entities. In addition, we can not use cell culture studies evaluate systemic toxic or efficacy effects, thus the use of animal models is unavoidable.
The implantation of tumours will be achieved under anaesthesia. The animals will receive analgesia post implantation and will be monitored closely by project members. Experienced technicians will monitor the animals and they will very early discover any sign of illness and take the decision of euthanasia, if necessary.
The smallest possible groups to provide a statistically significant power will be used.
Cancer in children and adolescents has an overall survival rate exceeding 80%. However, each year about 40 children and adolescents die from cancer in Norway, and many of the survivors suffer from long-term effects of cancer therapy. Furthermore, cancer in children differs from cancer in adults, and there is a great need for more research focusing on paediatric cancer. This includes the establishment of animal models specifically for rare or relapsed paediatric cancers.
2 Skadevirkninger
Our planned experiments must be classified as procedures of moderate severity: implantation of human cells will be performed subcutaneously, under anaesthesia and we expect the tumour to grow up to 1 cm3.
3 Forventet nytteverdi
By developing patient specific animal models we wish to both unravel knowledge on the specific tumour behaviour, including metastasis pattern, mutational distribution and tumour progression, as well as test new drugs or drug combinations that can benefit the patient.
4 Antall dyr og art
In this study we plan to use 850 male and female NSG immunodeficient mice to develop 25 preclinical models.
5 Hvordan etterleve 3R
Central to this application ins the development of relevant models for paediatric cancers and efficacy regimes. A relevant model will provide a better recapitulation of each patients disease heterogeneity, as well as displaying the variance between patients. These mice are the only animals which will successfully engraft a manner of human cell lines and patient material, essential to development of therapeutics. The only in vitro alternative is the use of cell lines and primary patient material in culture. However , these results do not always translate into efficacy in intact biological entities. In addition, we can not use cell culture studies evaluate systemic toxic or efficacy effects, thus the use of animal models is unavoidable.
The implantation of tumours will be achieved under anaesthesia. The animals will receive analgesia post implantation and will be monitored closely by project members. Experienced technicians will monitor the animals and they will very early discover any sign of illness and take the decision of euthanasia, if necessary.
The smallest possible groups to provide a statistically significant power will be used.