Targeting secreted factors in endocrine resistant breast cancer therapy

Albany College Of Pharmacy, Albany NY

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Abstract

Abstract/Summary: Various types of endocrine therapy have been used for postmenopausal women with early stage breast cancer. These therapies are safe and effective, but initially responsive breast tumors often develop resistance and eventually recur. Since a communication between tumor and tumor circumstance plays an important role to grow tumor and spread tumor to secondary organs, we examined the communication of endocrine resistant breast cancer with stroma which is the part of a tissue or organ that has a connective and structural role in cancer. We established four different endocrine resistant breast cancer cell lines and examined the communication of these cells with four stromal cells. We found that CCL5 and endoglin might play an important role in endocrine resistant breast cancer. Thus, we will 1) Investigate the role of CCL5 and endoglin in the crosstalk between ERBC cells and stromal cells, 2) Unveil the mechanism of the upregulated CCL5 and endoglin in crosstalk between ERBC and stroma, and 3) Develop therapeutic strategies to block the paracrine interaction between the stromal cell and ERBC cell. We will investigate which secreted factors could serve as a key regulator in the transition of breast cancer cells to endocrine resistance and gaining of an aggressive phenotype. Further, secreted factors from the communication between endocrine resistant breast cancer and stroma might prove to be an attractive target for breast cancer drugs. Most of the cancer drugs in use currently have been developed to directly impact tumor cells. These drugs do not do much to block signals coming from tumor circumstance. Our proposed investigation will give us a small list of the most potent of these signals. Drugs, some of which we will identify here, and others that will have to be developed, that block these signals could limit the ability of the tumors to spread to secondary organs, which should result in overall survival gains for patients.