Investigation for drug combinations for combinatorial treatment for HER2 positive cancers
Breast cancer is the most common cancer type among women in Norway with 3322 new cases in 2014. It is a heterogeneous disease consisting of several different sub-groups with distinct molecular profiles and different outcome. One group of patients counting for 20% of all breast cancers is characterized by an overexpression of the epidermal growth factor receptor 2, ERBB2/HER2.
New promising therapies using small molecules targeting HER2 and its signalling pathways have emerged during the last decade. However, not all HER2 positive patients respond to treatment, and resistance to treatment is common. It is therefore important do find new treatment options for this group of patients.
We have previously used well-characterized cell lines and performed high-throughput screens to identify regulatory mechanisms and/or promising drug combinations for Her2 positive tumors. In that drug-screen dasatinib was identified as a promising compensatory drug with trastuzumab and lapatinib. The aim of this study is to evaluate different drug combinations for combinatorial treatment for HER2 positive cancer.
For the mice in the treatment experiment it will be Moderat belastende . The mice will be given sc and iv injection and oral gavage. Tumor size will be measured. The mice will be subjected to injection of human cells, bi-lateral tumor growth and daily drug administration. When designing the experimental setup for this application the three R's were applied in the design of the experimental outline. By using drug screens in cell lines prior to in vivo experiments we have a well founded reason for investigating these drug combinations further and bu using cell lines for screening we can limit the number of animals used significantly. For this application we apply for 128 Nude mice.
We will treat mice with Her2 positive xenografts with lasatinib, lapatinib and trastuzumab, alone or in different combinations and evaluate the effect of mono treatment of these drugs and when given in combination.
New promising therapies using small molecules targeting HER2 and its signalling pathways have emerged during the last decade. However, not all HER2 positive patients respond to treatment, and resistance to treatment is common. It is therefore important do find new treatment options for this group of patients.
We have previously used well-characterized cell lines and performed high-throughput screens to identify regulatory mechanisms and/or promising drug combinations for Her2 positive tumors. In that drug-screen dasatinib was identified as a promising compensatory drug with trastuzumab and lapatinib. The aim of this study is to evaluate different drug combinations for combinatorial treatment for HER2 positive cancer.
For the mice in the treatment experiment it will be Moderat belastende . The mice will be given sc and iv injection and oral gavage. Tumor size will be measured. The mice will be subjected to injection of human cells, bi-lateral tumor growth and daily drug administration. When designing the experimental setup for this application the three R's were applied in the design of the experimental outline. By using drug screens in cell lines prior to in vivo experiments we have a well founded reason for investigating these drug combinations further and bu using cell lines for screening we can limit the number of animals used significantly. For this application we apply for 128 Nude mice.
We will treat mice with Her2 positive xenografts with lasatinib, lapatinib and trastuzumab, alone or in different combinations and evaluate the effect of mono treatment of these drugs and when given in combination.