School of Medical Sciences


New inhibitors of cancer cell signalling pathways

Tumour cells often have altered gene defects that contribute to their ability to resist anticancer therapy. We are currently working in conjunction with the Medicinal Chemistry group on the development of drugs that are able to counter this resistance.

 

p53


The first target protein is the so-called p53 protein, which coordinates many of the cellular responses to stress. About 50% of human cancers have a genetic defect in the gene for p53 and in most cases this leads to a mutant protein that has a change in a single amino acid. We are using a series of cultured cell lines to investigate new drugs that appear to reconstitute the normal activity of the mutant protein.

 

PI3K


The second target is the so-called PI3K enzyme, which plays a central role in cellular metabolism and survival. We are investigating the effects of new inhibitors of this enzyme, again on a series of human tumour cell lines that have different genetic effects, leading to altered function of the PI3K enzyme.

Selected recent publications


Baguley BC. Multidrug resistance in cancer. Methods Mol Biol 2010; 596:1-14.

Ramachandran A, Marshall ES, Love DR, Baguley BC, Shelling AN. Activin is a potent growth suppressor of epithelial ovarian cancer cells. Cancer Lett 2009; in press. PMID:  19493612

Baguley BC, Marshall EM. The use of human tumour cell lines in the discovery of new cancer chemotherapeutic drugs. Expert Opinion Drug Discovery 2008; 3: 153-161.

Kendall JD, Rewcastle GD, Frederick R, Mawson C, Denny WA, Marshall ES, Baguley BC, Chaussade C, Jackson SP, Shepherd PR. Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110alpha inhibitors. Bioorg Med Chem 2007;15: 7677-7687.  PMID: 17869522