Ongoing Research

Currently, research is being conducted to figure out the relationship between the ACRBP gene/protein and all the other proteins and genes that it interacts with in order to help cancer cells resist being poisoned by the chemotherapy drug paclitaxel. Because the gene for resistance had been identified from the whole-genome assay it was much easier to isolate the protein from the cell. The protein was isolated from the cell, along with a few other proteins it was interacting with, and a machine called a Mass Spectrometer was used to identify the proteins that were interacting with it. With a number of proteins to focus on, researchers are currently trying to understand the way the proteins interact with each other, and with the genes responsible for making them. To explore the relationships between the components researchers are conducting a number of careful studies that involved removing specific proteins via RNA interference and/or increasing the production of proteins by adding extra gene copies.


Modeling in Mice

When performing research, most of the investigations cannot occur in real, live human beings with cancer, for obvious reasons. Instead, scientists utilize model organisms that have many similarities with human beings for the purpose of the tests being performed, but are much easier to manage, have faster lifespan, and show the effects of changes more quickly. While research up to this point has made it apparently clear that removing the ACRBP protein from cells causes them to be killed much more easily by chemotherapy, it has been done on cell lines in a dish. To show that this is not simply a strange effect of the cell lines, testing on mice was done


Mice were injected with cancer and were treated with low doses of the chemotherapy drug paclitaxel and either had a functional copy of ACRBP or no ACRBP. The lifespan of the groups of mice is shown in the chart, and, as can be clearly seen, removing ACRBP grants increased survival chances with cancer and once appropriate targets are chosen, drugs can be developed to mimic the effect of removing ACRBP by choosing the appropriate protein targets for drugs to interfere with. Such drugs would mimic the effect of removing ACRBP and, when taken with regular chemotherapy, would drastically improve the treatment for patients.

 

Protein Interactions

In order to create drugs that mimic the removal of ACRBP, we need to understand the process by which ACRBP affects the cell. While the interaction of a few proteins may at first seem simple, the behavior of ACRBP that causes resistance to chemotherapy seems to involve several proteins and several genes. The exact names of all the involved proteins and genes are complicated and the interactions are not yet fully understood, which is why we are doing research to understand the interaction. A picture representing a possible series of interactions that results in a final protein that causes chemotherapy resistance is shown. Beacuse of the wide variety of interactions that end up occuring in this pathway there are a large number of protein targets for drugs designed to remove the benefit that ACRBP gives cancer cells and increase the effectiveness of cancer treatment. Once the process is well understood the process of Drug Development is the next step.


How did Researchers Get Here? What Comes Next?