Drug Target Discovery
Dr Spiros Linardopoulos, Team Leader for Drug Target Discovery.
Overview
Mitosis is structurally the
most dynamic phase of the cell cycle, as sister chromatids are
irreversibly segregated to daughter cells. Defects in mitotic spindle
assembly and in the checkpoints that normally maintain the fidelity of
this process can lead to chromosomal instability and cancer.
The fidelity of chromosome segregation is monitored by mitotic
checkpoints that delay entry into mitosis until all of chromosomes have
made correct attachments to spindle microtubules. During this complex
process, protein kinases play important roles in promoting or retarding
transitions between different stages and checkpoints of the cell cycle.
We aim to further understand mitotic control and use this information to
identify and validate mitotic regulators as targets for cancer therapy.
Our focus
The
research of the Cancer Drug Target Discovery laboratory has focused on
the mitotic kinases Aurora-A and Mps1. Aurora-A kinase has been found to
be amplified in more than 50% of primary colorectal cancers and up to
20% of primary breast tumours as well as in breast, ovarian, colon,
prostate, and cervical cell lines. Mps1 is a mitotic checkpoint kinase. Increased Mps1 expression has been found in multiple
different types of human cancers including breast cancer. The
over-expression of these kinases and the association with genetic
instability in tumours has made these genes attractive targets for
anticancer drug discovery.
