Oncology Frontier: How does that translate then to use in the clinic?

　　《肿瘤瞭望》：这些研究结果应如何被转化并应用于临床实践？

　　Dr. Ellis: Drugs that degrade the ER and will treat mutants so theoretically ER degradation agents may actually prevent the development of mutations. If you are targeting and a mutation arises by using a drug that would naturally inhibitor it and resistance should not occur， so if you think about it， that is how we cured HIV by combining multiple drugs with different mechanisms. The prognosis for HIV has been dramatically altered because those multiple targeting approaches makes it very difficult for the virion to evolve a resistance through mutations that require 3 separate mutations to deal with 3 separate drugs. I think that is kind of the idea we are going with. The translocations however are not targetable by conventional endocrine therapy and so we may be able to target downstream. We serve an example where downstream we could inhibit with a drug called Palbociclib which restores the tumor’s suppressing function of Rb and that is enough for the tumor to actually respond. We sort of drug the consequences of the translocations successfully.

　　Ellis博士：可降解雌激素受体的药物能够治疗上述突变，因此从理论上来说雌激素受体降解剂可预防上述突变。在靶向治疗时突变发生，应用抑制突变的药物则不会发生耐药。这也是为什么用多种不同机制的药物联合治疗HIV。这种方法使病毒难以通过突变而耐药，因为要应付3种药物就需要3种突变，所以HIV患者的预后大幅因此改善，我认为这是我们未来需要研究的方向。但是，传统的内分泌治疗无法以基因易位为干预靶标，所以我们可能需要针对易位的下游进行干预。例如，我们可以用Palbociclib药物恢复肿瘤抑制因子Rb的功能，从而对下游进行干预，使肿瘤对治疗有反应，药物效果很好。