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

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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.