Metastasis is responsible for more than 90% of deaths among cancer patients. It is a highly complex process that involves the interplay between cancer cells.
Recently, cancer stem cells (CSCs) have been thought as the seeds of tumorigenesis. However, the relationship between CSCs and circulating tumor cells (CTCs) and the mechanism by which CSCs lead to colonization are still unclear. Here, the applicant plans to trace the changes in CSCs during tumorigenesis and metastasis.
In circulation, most CTCs fail to disseminate. While our knowledge of the factors that determine survival is increasing, very little is known about where the disseminated survivor cells come from i.e., the issue of origin. or what makes CTCs survive ,i.e the issue of environment.
How can we view cancer and win it ?
Cancer therapy may not be the issue of killing the disease cells. We need to change the paradigm for the war.
Our researches will try to identify mediators of metastasis that are common to different organ sites and tumor types. The topic of organ-specific metastasis has revealed that metastatic colonization is different event between organs, by association of different molecules based on seed and soil theory. Thus, late stage of colonization is unlikely to find common target to suppress metastasis. Rather, fate or metastatic potential of CTC may be determined at relatively early stage with CSC. However, it is not clear whether CSCs are derived from normal stem cells or by mutation accumulation in non-stem tumor cells. In addition, gene expression patterns and additional mutations that differentiate normal stem cells, cancer stem cells, and non-stem tumor cells have not been examined thoroughly. Furthermore, the difference in metastasis ability among cell types is not clear.
We have focused on breast cancer cells which metastasize to brain since it is known that metastasizing to brain is particularly fatal to patients as the treatment becomes difficult and complex. Thus, to find more effective ways to treat brain metastasis of breast cancer cells, we have performed in-silico analyses for novel targets discovery, and for repurposing of existing drugs. We examined differential expressed genes of breast cancer when cells are metastasizing to brain by using meta-analysis of three publicly available datasets.