A chemical biology approach to the study of amoeboid invasion by tumour cells

癌症之所以致命，是因为它们能够在身体周围移动，侵入其他器官，在那里生长，导致器官衰竭。其中一种方法是通过产生能够穿透身体基质的酶，让肿瘤细胞强行进入。这些酶代表了一种潜在的药物靶点，但到目前为止，还没有候选药物进入临床。其中一个原因可能是细胞能够改变它们入侵的方式。这些细胞不是用蛮力来切割基质，而是能够改变它们的形状，挤进基质，像被称为变形虫的单细胞生物一样移动。这种变形虫的入侵仍处于非常初步的研究阶段，但一种从海绵中分离出来的天然产物，被称为neoppetrosiamde，已被证明可以抑制这种影响。利用天然产物作为工具可以帮助我们识别涉及变形虫入侵的过程，我们打算制造并研究其在生物系统中的作用。我们还将制作类似物，对结构进行单一改变，以确定抑制的要求，并最终设计新的治疗剂。

Cancers kill because they are able to migrate around the body and invade other organs, growing there and causing the organ to fail. One way they do this is by producing enzymes that are able to cut through the matix of the body and allow the tumour cells to force their way in. These enzymes represent a potential drug target, but so far, no candidate has made it into the clinic. One reason for this may be that the cells are able to change the way they invade. Instead of using brute force to cut their way into the matrix, the cells are able to alter their shape and squeeze their way into the matrix, moving like the single celled organism known as an amoeba. This amoeboid invasion is still under very preliminary study but a natural product, isolated from a marine sponge and called a neopetrosiamde, has been shown to inhibit this effect. Using the natural product as a tool may help us to identify processes involved in amoeboid invasion and we intend to make this and study its effects in biological systems. We will also make analogues, with single changes to the structure, to identify the requirements for inhibition and ultimately to design new therapeutic agents.