RATHER is a consortium project funded by the European Commission's 7th Framework Programme of Research and Development. The project will focus on several key aspects of breast cancer research, and will involve the combined efforts of six universities and two biomedical companies. RATHER commenced in January 2011, and will operate for a period of five years.
The project will investigate two specific difficult-to-treat subtypes of breast cancer.
- Invasive Lobular Carcinoma (ILC) is a type of cancer that arises within the milk-producing lobules of the breast. It accounts for approximately 10% of cases of breast cancer globally.
- Triple Negative (TN) breast cancer is a subtype that lacks the estrogen, progesterone and HER2 receptors. It accounts for approximately 15% of cases.
At present, no targeted therapies are available for either of these diseases.
The RATHER consortium aims to better our understanding of these cancers by applying state-of-the-art investigative techniques to 300 clinical samples from patients with these diseases (150 ILC and 150 TN). These samples will be examined in fine detail using a wide variety of technology platforms. This research will enable us to identify the fundamental differences between normal and diseased breast tissue. Our hope is that some of these differences/alterations will prove to be drivers of disease – meaning that they are involved in causing the disease, as opposed to being random side-effects of the condition. Identifying driver alterations is an important step in the fight against cancer, since they represent promising therapeutic targets.
RATHER is particularly interested in a subset of human proteins known as kinases. These are important molecules within the body that play a key part in many physiological pathways. In recent years, it has been established that alterations to one or more of the 500 human kinases can play a pivotal role in cancer. RATHER aims to identify kinase alterations that are specific to ILC and TN. This information will allow us to select, in a rational manner, one or more kinase inhibitor drugs that can be used to treat these diseases.
Even within well-defined subtypes of breast cancer like ILC and TN, there are likely to exist a number of different driver alterations. For example, two patients might exhibit different kinase alterations, and so respond to different kinase inhibitor drugs. RATHER will address this issue by developing molecular diagnostic tests to accompany the alterations that we target. These tests will allow us to establish the particular alteration(s) a patient exhibits, and therefore allow us to choose appropriate therapies for that patient.
Once we have identified promising kinase alterations and their corresponding kinase inhibitors, we will initiate a phase I/II clinical trial to examine patient responses to these drugs in a clinical setting. Our molecular diagnostic tests will be used to select patients for this trial, thus ensuring that only patients who might benefit from the drugs will be enrolled.
As encapsulated in the project title, an overarching theme of the project is to develop therapies using a rational approach. We will systematically identify disease-specific alterations, and then choose suitable drugs that are known to target these alterations. This approach represents a departure from traditional large-scale exploratory drug screens, and brings us closer to the ideal of personalised medicine, where we can use diagnostic tests to choose the best possible drugs for each individual patient. Therefore, in addition to widely expanding our knowledge of ILC and TN, we are confident that the RATHER approach will serve as a model for future investigations in the fight against disease.
Targeting the drivers of difficult-to-treat breast cancers
HORIZON 2020, World Cancer Day, 4 February 2015. (more)