关键词：乳腺癌;凋亡;基因;基因;转移;耐药性;治疗
摘 要：Breast cancer is the most common cancer in women and the second deadliest. There is a great need to finding new targeted therapies and to improve the efficacy of existing therapies. The TNF Related Apoptosis Inducing Ligand (TRAIL) pathway is part of the body s natural tumor surveillance program, preventing formation of tumors and metastasis while sparing normal cells. The TRAIL pathway has been exploited in clinical trials but resistance to TRAIL is common, limiting the efficacy of therapy. The mechanisms underlying TRAIL resistance are largely unknown and there is of yet not a good way to screen for TRAIL sensitivity. We have found that the gene Six1, which is overexpressed in over half of all breast cancers and in as much as 90of metastatic lesions, confers resistance to TRAIL. In addition, by screening a genome wide shRNA library we have identified 4 novel TRAIL resistance gene including the solute carrier family 26 (sulfate transporter), member 2 (SLC26A2). The role of these genes in TRAIL resistance and metastatic spread are being investigated, with the ultimate aim of identifying TRAIL resistance and circumventing it through targeted combination therapies.