Breast cancer cell/adipocyte crosstalk and Tamoxifen Resistance: a potential role for IGF-1/TXNIP axis

Although endocrine therapy (ET) has improved the outcomes of Estrogen Receptor (ER) a-positive breast cancer (BC) patients, resistance to these treatments remains a major challenge. Evidence proved that a reduced response to ET is tightly dependent on the surrounding microenvironment and on the host characteristics. Indeed, several studies have highlighted that obesity, in addition to promote BC development and progression, represents a heavyweight player driving ET resistance. Here, we evaluated the influence of adipocytes and their secretome on the efficacy of ET. Our findings bring insights on adipocytes and mammary cancer cell crosstalk during endocrine therapy, suggesting the possibility to target IGF-1/TXNIP axis to block this harmful connection, especially in obesity settings. Overall design: Comparative transcriptomic profile between MCF-7 Tamoxifen-resistant (TR) cells untreated or treated with conditioned medium derived from 3T3L1 mature adipocytes.