Oncology Frontier: Dr. Ellis， it is reported that endocrine therapy resistant estrogen receptor positive breast cancer is the most common cause of breast cancer death. Could you talk about some of the pathways that are involved in the endocrine therapy resistance?

　　《肿瘤瞭望》：有研究表明，雌激素受体（ER）阳性乳腺癌的内分泌治疗耐药是目前乳腺癌死亡的最常见原因。您能否谈一下哪些信号通路参与了内分泌治疗耐药机制？

　　Dr. Ellis: Well I would be happy to do that. People I think for a while， lost sight of the fact that the majority of deaths from breast cancer are in patients who has tumors that express the estrogen receptor. The breast cancer that is receptor positive typically has a lower initial relapse rate than patients with for example， triple negative disease or HER2 positive disease but that relapse rate is very persistent over a very long period of time with relapses and death up to 20 years is not that uncommon. Once you add up all the deaths from hormone receptor positive breast cancer over a 20 -year period， they will exceed the number of deaths from HER2 positive or triple negative breast cancer. We do have a very large unmet need. With respect to the pathways， in my talk today I focused on six signaling nodes that I think are very targetable and perhaps we might be able to combine inhibitors of 3 or more of these nodes to create the kind of therapeutic success we are looking for. The nodes are of course， estrogen receptors itself， as well as PI3 Kinase， MAP kinase， receptor tyrosine kinases， and regulation of the tumor suppressors Rb and P53.When we sift through all the genomic information we can come to the conclusion that the heterogeneity of hormone receptor positive breast cancer and sensitivity and resistance is likely to evolve around how exactly these six nodes are being perturbed by the recoding events that generate breast cancer.

　　Ellis博士：我非常愿意谈一下这个问题。我认为有时人们会忽视“大多数因乳腺癌而死的患者其肿瘤雌激素受体表达”这一事实。与三阴性乳腺癌或HER-2阳性乳腺癌等相比，ER阳性乳腺癌的最初复发率低。若把20年的ER阳性乳腺癌所致死亡累加，则其会超过HER-2阳性或三阴性乳腺癌所致的死亡。ER阳性乳腺癌的治疗效果差强人意。就信号通路而言，我今天在会上的演讲重点强调的是我认为非常具有靶向性的6个信号节点，如若能将抑制剂与3个或3个的信号节点结合，则有望取得满意的治疗效果。具体来说，这些信号节点主要包括ER本身、PI3K、MAPK、受体酪氨酸激酶以及具有肿瘤抑制调节作用的Rb及P53。对全基因组信息进行筛选可见，ER阳性乳腺癌有异质性，触发乳腺癌的重新编码干扰这6个节点，导致了ER阳性乳腺癌内分泌治疗敏感和耐药。