Cell Cycle Control Team
Team Leader: Dr Michelle Garrett
Location: Haddow Laboratories, Sutton
Section: Cancer Research UK Cancer Therapeutics Unit
One of the principal characteristics of human cancer is the ability of cells to proliferate in an uncontrolled manner. At the heart of this process is the cell division cycle and when not controlled correctly, it can be one of the underlying causes of cancer. A number of signalling pathways can act on the cell division cycle, either through growth factor regulation during G1 or through activation of cell cycle checkpoints in response to DNA damage and we are particularly interested in how these pathways may be targeted for the treatment of cancer.
A key aim of the this team is therefore to discover and develop new drugs that act on the molecular components of the cell division cycle and the signalling pathways through which it is regulated.
We are currently participating in a number of drug discovery and development programs including those that target the serine/threonine kinases PKB /AKT, CHK1 and CHK2. A key role of the team in this process is to understand at the molecular level the mechanism of action of compounds developed on these programs. An important part of this research is the ability to study the effects of these compounds on tumour both in vitro (through cell lines) and in vivo. For example, for the PKB/AKT drug discovery and development program known markers of PKB inhibition are the phosphorylation status of substrate proteins such as GSK3beta, PRAS40 and TSC2 (tuberin). Such potential markers of drug effect are often referred to as pharmacodynamic (PD) biomarkers and are becoming established as an important part of both preclinical and clinical drug development. The team has therefore been carrying out PD biomarker discovery and development for its ongoing preclinical drug discovery projects including PKB/AKT, CHK1 and CHK2. This has led to the recent establishment of the GCLP Biomarker Group, within the Cell Cycle Control team. This group specifically identifies and develops PD biomarkers for Phase I clinical trials and therefore operates within the guidelines for Good Clinical Laboratory Practice (GCLP).
Aims
- To discover and develop new drugs that act on molecular components of the cell division cycle and its associated pathways and to understand the mechanism of action of these drugs.
- To identify and develop PD biomarkers to be used in both preclinical drug development and Phase I clinical trials of these new molecular targeted agents.
In the Cancer Research UK Cancer Therapeutics Unit
