As a field we have made tremendous strides in treating breast cancer,with a decline in the past 30 years of overall breast cancer mortality.However,this progress is met with little affect once the disease spreads beyo...As a field we have made tremendous strides in treating breast cancer,with a decline in the past 30 years of overall breast cancer mortality.However,this progress is met with little affect once the disease spreads beyond the primary site.With a 5-year survival rate of 22%,10-year of 13%,for those patients with metastatic breast cancer(mBC),our ability to effectively treat wide spread disease is minimal.A major contributing factor to this ineffectiveness is the complex make-up,or heterogeneity,of the primary site.Within a primary tumor,secreted factors,malignant and pre-malignant epithelial cells,immune cells,stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis.Furthermore,heterogeneity contributes to our lack of understanding regarding the cells'remarkable ability to undergo epithelial/non-cancer stem cell(CSC)to mesenchymal/CSC(E-M/CSC)plasticity.The enhanced invasion&motility,tumor-initiating potential,and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis.While most work trying to understand E-M/CSC plasticity has been done on malignant cells,recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process.Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor.Moreover,we will discuss how one may potentially target these populations,ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.展开更多
文摘As a field we have made tremendous strides in treating breast cancer,with a decline in the past 30 years of overall breast cancer mortality.However,this progress is met with little affect once the disease spreads beyond the primary site.With a 5-year survival rate of 22%,10-year of 13%,for those patients with metastatic breast cancer(mBC),our ability to effectively treat wide spread disease is minimal.A major contributing factor to this ineffectiveness is the complex make-up,or heterogeneity,of the primary site.Within a primary tumor,secreted factors,malignant and pre-malignant epithelial cells,immune cells,stromal fibroblasts and many others all reside alongside each other creating a dynamic environment contributing to metastasis.Furthermore,heterogeneity contributes to our lack of understanding regarding the cells'remarkable ability to undergo epithelial/non-cancer stem cell(CSC)to mesenchymal/CSC(E-M/CSC)plasticity.The enhanced invasion&motility,tumor-initiating potential,and acquired therapeutic resistance which accompanies E-M/CSC plasticity implicates a significant role in metastasis.While most work trying to understand E-M/CSC plasticity has been done on malignant cells,recent evidence is emerging concerning the ability for pre-malignant cells to undergo E-M/CSC plasticity and contribute to the metastatic process.Here we will discuss the importance of E-M/CSC plasticity within malignant and pre-malignant populations of the tumor.Moreover,we will discuss how one may potentially target these populations,ultimately disrupting the metastatic cascade and increasing patient survival for those with mBC.
