The MCCS team introduces itself
The Molecular control of cell signaling (MCCS) research team is a benjamin among other sites within the FNUSA-ICRC. What is the focus of his work and what he plans for the future, described us team leader Dr. Jaeyoung Shin.
The FNUSA-ICRC creates a new interdisciplinary platform linking the scientific and research areas with medical science. It offers opportunity for schools, hospitals, researches and scientific teams to present their outputs to each other. Our Molecular Control of Cell Signaling research team (MCCS) will have the opportunity to acquire new inputs and partners for our future projects. The FNUSA-ICRC will be able to see our activities and opened or planned projects.
The treatment of metastatic cancer has undergone a paradigm shift in the last couple of years. The identification of specific receptor of signaling molecules in tumors gives the promise of cellular signaling molecular-based control strategies, which are commonly referred to as ‘targeted therapies’. These new generations of targeted therapies can control tumor growth for several months and may replace unspecific cytotoxic chemotherapies for many cancer types. However, full curings by molecular modification responses are rare, due to the emergence of aggressive, drug-resistant clones that drive relapse and rapidly form new metastases. As a result, cure rates and long-term survival rates of metastatic patients treated with targeted therapies remain disappointingly low.
To better understand the clinical emergence of resistant cells, our work focuses on the poorly understood events during tumorigenesis. By combining the power of experimental model systems, in situ gene expression profiling techniques, and computational analysis, we assume that targeted therapy with kinase inhibitors induces a complex network of secreted signals in breast cancer and lung adenocarcinoma cells.
This response called therapy-induced secretome not only enhances the survival of signaling molecular transfected cells, but also stimulates the proliferation, invasion, and metastasis of molecular-resistant clones that are lurking in the background of the tumours. We also suppose that the tumours in our animal models act as potent ‘RNAi’ to attract molecular-resistant cells from the circulation. This process called knockdown by RNAi, could add an additional layer of complexity to the treatment of relapsed patients by targeted therapy.
The addition of MAPK (Mitogen-Activated Protein Kinases) signaling inhibitors blunted the growth and metastasis of resistant cancer cells in animal models. These experiments indicate that this drug development by molecular modification is a potential strategy to delay tumour relapse in patients. Even more importantly, our study started to expose the significant changes in tumours treated with targeted therapies. These changes are still largely unexplored and are expected to have a major influence on immunotherapy efficacy in combination with other curing approaches.