Development of new therapies for drug resistant melanomas
Background
Melanoma is an aggressive malignancy, which has a poor prognosis once the tumour has metastasized. New therapies targeting BRAF and MEK have shown increased survival of melanoma patients. However, the majority of patients develop resistance to these targeted therapies after a few months.
To understand the molecular mechanisms behind treatment resistance as well as to find new therapies, we have developed several melanoma cell lines which are resistant to BRAF and MEK inhibitors. The cell lines are currently being characterized in vitro, and will be screened in vitro using drug libraries, to find promising compounds for treating treatment resistant melanoma.
In this project, we will establish mouse models for metastatic melanoma using naive and treatment resistant cell lines. These models will then be used to study potential effects of promising drug compounds found in the in vitro drug screening experiments.
1. Aim of the research
To understand the molecular mechanisms leading to treatment resistance in melanoma patients, and to find new drugs which may overcome resistance and metastatic spread, which may lead to better treatment of this patient group.
2. Expected harm to the animals
We regard the burden to the animals to be of medium level, due to the intracardial injection procedure and the fact that the animals develop metastatic tumors in the brain over time. Regarding the burden to the animals during treatment, we regard this as being low. BRAF and MEK inhibitors are already tested in mouse experiments and drug toxicities are thus well characterised. When we find new drugs from the drug screening experiments, we will ensure that we administer drug doses well below toxic values to the animals, by studying what has been done previously in literature, and by performing pilot toxicity experiments if necessary.
3. Expected benefit for science and society
If successful, we hope to achieve a new and better treatment of cancer patients with treatment resistant and metastatic melanoma.
4. How many and kind of animals to be used
We plan to use up to a total of 456 nod/scid mice (male and female) in our experiments.
5. How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3D structural behavior and physiological conditions in animals, and these conditions are crucial for growth and metastatic spread of cancers in patients. Therefore, we are of the opinion that in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.
Melanoma is an aggressive malignancy, which has a poor prognosis once the tumour has metastasized. New therapies targeting BRAF and MEK have shown increased survival of melanoma patients. However, the majority of patients develop resistance to these targeted therapies after a few months.
To understand the molecular mechanisms behind treatment resistance as well as to find new therapies, we have developed several melanoma cell lines which are resistant to BRAF and MEK inhibitors. The cell lines are currently being characterized in vitro, and will be screened in vitro using drug libraries, to find promising compounds for treating treatment resistant melanoma.
In this project, we will establish mouse models for metastatic melanoma using naive and treatment resistant cell lines. These models will then be used to study potential effects of promising drug compounds found in the in vitro drug screening experiments.
1. Aim of the research
To understand the molecular mechanisms leading to treatment resistance in melanoma patients, and to find new drugs which may overcome resistance and metastatic spread, which may lead to better treatment of this patient group.
2. Expected harm to the animals
We regard the burden to the animals to be of medium level, due to the intracardial injection procedure and the fact that the animals develop metastatic tumors in the brain over time. Regarding the burden to the animals during treatment, we regard this as being low. BRAF and MEK inhibitors are already tested in mouse experiments and drug toxicities are thus well characterised. When we find new drugs from the drug screening experiments, we will ensure that we administer drug doses well below toxic values to the animals, by studying what has been done previously in literature, and by performing pilot toxicity experiments if necessary.
3. Expected benefit for science and society
If successful, we hope to achieve a new and better treatment of cancer patients with treatment resistant and metastatic melanoma.
4. How many and kind of animals to be used
We plan to use up to a total of 456 nod/scid mice (male and female) in our experiments.
5. How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3D structural behavior and physiological conditions in animals, and these conditions are crucial for growth and metastatic spread of cancers in patients. Therefore, we are of the opinion that in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.