Forsøksdyr: Therapeutic strategies against resistant and metastatic breast cancer (TheraMetBC)


Godkjenningsdato 18.06.2018

AIM OF STUDY:
Breast cancer is the most common cancer in women in Norway with approximately 10% of newly registered (approx.3500) cases per year (Kreftregisteret 2015 report). Patients with the aggressive disease, TNBC and metastatic breast cancer, receive chemotherapy. However, resistance often develops, emphasizing the need for other treatment options. In this project the aim will be to develop and investigate therapeutic strategies against treatment resistant and metastatic breast cancer. We aim to reveal their sensitivity to chemotherapy and response to biological inhibitors targeting the resistance mechanisms and investigate the molecular effects induced by the treatment.

ANIMAL WELFARE:
Animals will be given different chemotherapies and inhibitors alone or in combination that might lead to toxicity in the animals. The dosing of the compounds will be adjusted to an acceptable level with minimal and tolerable side effects. However, since some animals may experience toxicity, the experiments will be classified as moderately influencing animal welfare.

SCIENTIFIC VALUE:
Chemotherapy resistant breast cancer is a major clinical problem, and disclosing the involved biological mechanisms and, consequently, develop new effective treatment strategies would benefit a large group of patients. Information collected from our therapeutic studies in the PDX models will guide the selection of treatment strategies in clinical trials (to be developed by our research group in the near future) to combat treatment resistant disease in breast cancer patients.

NUMBER OF ANIMALS USED:
We apply for the use of 3504 nude mice over a period of four years.

PRINCIPLES OF REPLACEMENT (I), REDUCTION (II) AND REFINEMENT (III)

I) In vitro experiments using cell cultures can sometimes be an alternative in testing cancer treatment strategies, however they are often limited as a screening method for evaluating the treatment efficacy in farmacological relevant doses. However, to generate treatment data to support clinical testing animal studies must be performed.

II) We have conducted statistical power analyses to determine the minimum required sample sizes to obtain significant results.

III) Anaesthetic (Sevofluran/Zoletil) and analgesic (Temgesic/Marcain) regimes for pain relief are in place to reduce potential pain after implantation of tumor tissue. Appropriate experimental endpoints that allow for early intervention have been implemented to reduce animal suffering. Handeling of the animals will be performed by experienced personel so that the discomfort/stress to the mice will be at a minimum. The enviroment of the mice will be enriched with soft paper and plastic houses.