Therapeutic Strategies in Metastatic and Resistant Breast Cancer
The project idea is based on the fact that a significant number of breast cancer patients will acquire resistance and progress into metastatic disease. The overall aim of the project is thus to improve future breast cancer treatment by categorizing patients having developed resistance against standard therapy into new treatment groups based on biological traits gained in the tumor during earlier lines of treatment. The project receives funding from the Norwegian Cancer Society (2018-2021) and is composed of both clinical and experimental subprojects. The specific goals are:
- Identify molecular signatures predicting response to DNA-targeted therapy using longitudinal tumor samples from the clinical trial I-BCT1.
- Test hypotheses on mechanisms causing resistance by intervening corresponding pathways/microenvironmental interactions in patient-derived preclinical models, and unravel molecular portraits predicting response or activation of potential survival pathways (Project page)
- Identify novel targets to combat resistance utilizing resistant model systems (cell lines or PDX)
RESistance Under Combinatorial Treatment in ER+ and ER- Breast Cancer
RESCUER is a project which newly got funding from H2020 (PI Prof Vessela Kristensen) and join fifteen research groups in Europe and the US. The project is based on the same fundamental question as TheraMetBC; what to offer breast cancer patients that develop resistance?
The objective is to discover treatment combinations for individuals/subgroups of BC patients through the assessment and validation in vivo, in vitro and in silico of mechanisms of treatment resistance. RESCUER will integrate and analyze existing and newly generated clinical and multi-omic data and biological samples from ongoing clinical trials to identify the physiological characteristics of non-responders vs. responders and to suggest clinically effective personalized drug combinations. The group will be responsible for testing promising drug combinations in PDX-models.
Improved treatment of HER2-positive breast cancer
PI: Kristine K. Sahlberg, Vestre Viken
Clinical response to HER2 targeted treatment varies and we seek to increase our understanding of HER2 positive breast cancers and their response to treatment. Using in vitro models we will investigate the miRNAs role to modulate the response to HER2-targeted therapy by sensitization screens with drug treatments. Furthermore, drug sensitization by in vitro screening will be studied in a medium-throughput fashion and tested in mice. By integrating molecular profiling data from multiple levels from the same patients in larger cohorts, we will be able to study the molecular mechanisms in HER2+ cancer in detail in a systems biology approach and investigate the clinical relevance of our findings from the in vitro models.
The main goals of this project are:
- Investigate whether miRNAs sensitize HER2 positive cells to HER2 targeted treatment.
- Search for drug combinations for treatment for HER2 positive cancers.
Read more about these projects at The National Network for Breast Cancer Research.