Grant: Operating Grant

DNA sequencing technology has advanced in leaps and bounds during the last few years, and we can now sequence the genomes of tumour cells to identify the gene mutations contained within. Although this is a relatively new field, we are already making discoveries that have the potential to lead to new diagnostic tests and drug treatments for cancer patients. However, new sequencing discoveries will not make an impact on cancer treatment and outcomes without first undergoing extensive investigation and characterisation in the laboratory. We are now nearing the final stages of a sequencing survey of many hundreds of cancers of the breast, ovary, and uterus. We have discovered that many tumours contain mutations in genes called phosphatases. Phosphatases modify proteins within the cell to change their function and are known to control processes that are disrupted in cancer cells, such as cell growth and division. It is relatively easy to modify the effects of some phosphatases using chemicals, making them an attractive target for drug development. We propose to investigate the consequences of the phosphatase gene mutations that we have identified in tumours. First, we will check for mutations in these genes in a large number of additional breast, ovarian, and endometrial (uterus) cancers; the aim is to determine how common these genetic alterations are in each type of cancer, and whether they're associated with particular tumour sub-types. We will then determine how mutating the phosphatase genes affects the growth and division of cancer cells. Finally, we will identify genetic weaknesses that are unique to cancer cells that contain phosphatase gene mutations; this is the first step toward developing new anti-cancer drugs that specifically kill these tumour cells. By the end of this project we will know whether a treatment based on targeting mutated phosphatase genes is likely to be effective, and if so, which cancer patients would benefit the most.