Study Promises Better Treatment For Chemotherapy Resistant Breast Cancer
According to new study conducted at the University of Kentucky and published in the Journal of Clinical Investigation, scientists are at one step away from discovering new agents that may treat triple-negative forms of breast cancer, which are also know as basal-like carcinoma. Triple-negative breast cancer is a tumoral subtype which is not expressing on its surface estrogen, progesterone or HER2 receptors and is associated with early metastasis and chemotherapy resistance. This subtype of breast cancer occurs with increased frequency in women of young age.
Cancerous cells in their migration are using a program of cellular signaling called epithelial-mesenchymal transition which promotes cell migration and inhibit adhesion between cells, thus helping tumor cells to spread to other organs and to produce metastasis. This epithelial-mesenchymal transition program is very active during the process of tissue remodeling, in wound healing and during embryonic development.
Cells to form a histological structure express an adhesion molecule named E-cadherin which has the role to keep cells closely bind in a certain architectural structure specific to each tissue. In the case of epithelial-mesenchymal transition, in order for the cells to detach from each other and to spread to other body structures, expression of E-cadherin must be inhibited. This inhibition action is performed by an other protein called Snail which posses the capacity to suppress E-cadherin expression and to induce epithelial-mesenchymal transition in body cells. The way in which Snail proteins suppress the expression of E-cadherin is unclear, but scientists said that by understanding the molecular mechanism of epithelial-mesenchymal transition which is responsible for breast cancer metastasis will helpful to develop in the future drugs which are capable to disrupt this cellular program.
Researchers also observed that to be active Snail proteins must interact with a chromatin modifying enzyme called G9a. This chromatin modifying enzyme posses the capacity to modify the structure of genes that express E-cadherin, thus down-regulating the expression of E-cadherin. This findings about Snail proteins and G9a interaction are very important for triple-negative breast cancer because this interaction represents a determinant factor in metastases occurrence.
“This finding has significant clinical ramification, because chemical compounds or agents that can disrupt the interaction of Snail with G9a will have a great therapeutic potential of treating triple-negative breast cancer. Investigators at the Markey Cancer Center are currently exploring this idea and are keen to develop drugs that can treat triple-negative breast cancer.”, scientists said.
Triple-negative breast cancer is a molecular subtype of breast cancer which is not expressing estrogen, progesterone and HER2 receptors on its surface. This tumoral subtype is associated with poor prognosis because produces early metastasis, cancer cells are unresponsive to conventional chemotherapy and affects manly young women.
“An understanding of the mechanism underlying the biology of metastasis in triple-negative breast cancer will provide novel therapeutic approaches to combat this life-threatening disease,” researchers added.