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
