The cell cycle, the process by which cells progress and divide, lies at the heart of cancer. In normal cells, the cell cycle is controlled by a complex series of signaling pathways by which a cell grows, replicates its DNA and divides. This process also includes mechanisms to ensure errors are corrected, and if not, the cells commit suicide (apoptosis). In cancer, as a result of genetic mutations, this regulatory process malfunctions, resulting in uncontrolled cell proliferation.

Cyclacel’s drug discovery and development programs build on recent scientific advances in understanding these molecular mechanisms. Through our expertise, we are developing cell cycle-based, mechanism-targeted cancer therapies that emulate the body’s natural process in order to stop the growth of cancer cells. This approach can limit the damage to normal cells and the accompanying side effects caused by conventional chemotherapeutic agents.

Professors Sir David Lane and David Glover, two of our key scientists, have built a leading position in cell cycle drug discovery and development. Sir David discovered the p53 protein, a key regulatory gene that malfunctions in about two-thirds of cancer patients. David Glover discovered several genes (Aurora and Polo kinases) that drive mitosis and that in mutated form are linked to many cancers.

Cyclacel is developing a large pipeline of drugs that target multiple, distinct points in the cell cycle. To learn more about the cell cycle, see below.

Additional Information
The cell cycle involves a complex series of molecular and biochemical signaling pathways. As illustrated in the diagram above the cell cycle has four phases:

• the G1, or gap, phase, in which the cell grows and prepares to synthesize DNA;
• the S, or synthesis, phase, in which the cell synthesizes DNA;
• the G2, or second gap, phase, in which the cell prepares to divide; and
• the M, or mitosis, phase, in which cell division occurs.

As a cell approaches the end of the G1 phase it is controlled at a vital checkpoint, called G1/S, where the cell determines whether or not to replicate its DNA. At this checkpoint the cell is checked for DNA damage to ensure that it has all the necessary cellular machinery to allow for successful cell division. As a result of this check, which involves the interactions of various proteins, a ‘‘molecular switch’’ is toggled on or off. Cells with intact DNA continue to S phase; cells with damaged DNA that cannot be repaired are arrested and ‘‘commit suicide’’ through apoptosis, or programmed cell death. A second such checkpoint occurs at the G2 phase following the synthesis of DNA in S phase but before cell division in M phase. Cells use a complex set of enzymes called kinases to control various steps in the cell cycle. Cyclin Dependent Kinases, or CDKs, are a specific enzyme family that use signals to switch on cell cycle mechanisms. CDKs themselves are activated by forming complexes with cyclins, another group of regulatory proteins only present for short periods in the cell cycle. When functioning properly, cell cycle regulatory proteins, including CDKs and cyclins, act as the body’s own tumor suppressors by inducing the death of damaged cells. Genetic mutations causing the malfunction or absence of one or more of the regulatory proteins at cell cycle checkpoints can result in the ‘‘molecular switch’’ being turned permanently on, permitting uncontrolled multiplication of the cell, leading to carcinogenesis, or tumor development.