Cancer Biology and Anti-Cancer Agents

'Metastasis' refers to spreading of cancer to different parts of the body and the appearance of secondary tumours.

Angiogenesis is the term used to indicate the growth of new blood vessels. It is a normal and vital process in growth and development as well as in wound healing.

 Depsipeptide is derived from a bacterial strain and is reduced to an active compound that promotes apoptosis and inhibits cell proliferation and angiogenesis.

Busulfan acts as an alkylating agent. It contains two sulfonyloxy groups, which act as good leaving groups when the drug reacts with a nucleophile.

ADEPT stands for antibody-directed enzyme prodrug therapy entangling the association of an enzyme to an antibody. It is the use of monoclonal antibodies (or mAb) to specifically bind to target cells or proteins.

'Angiostatin' is endogenously produced in the tumor 'stroma'. Therefore, the circulating levels can control metastatic cell proliferation until a primary tumor is removed. Angiostatin inhibits angiogenesis.

Chain cutting agents usually bind to DNA and generate radical species, which result in cutting of the DNA chain.

Integrins are a family of transmembrane glycoprotein receptors that mediate cell-matrix. They are involved in the anchoring of cells to an extracellular matrix. They affect tumour progression, which has made them an appealing target for cancer therapy.

Cyclophosphamide can be taken orally because it is non-toxic to the gut wall.

The binding site of receptors is analogous to the active site of enzymes. However, no reaction is catalysed. 

TP53 protein is normally present at very low levels in the cell because it is broken down very quickly after its synthesis. The p53 gene is a tumour suppressor gene, which is inactivated in at least 50% of all cancers. Its role is to prevent the replication of cells with damaged DNA.

The ras gene codes for a GTPase switch protein, which forms part of a growth factor signalling pathway. Stimulation of this protein through an occupied growth factor receptor causes it to activate by exchanging a molecule of GDP for GTP. The activated ras protein then activates downstream proteins, which ultimately activates transcription factors. Normally, the ras signal is self limiting because the protein has intrinsic GTPase activity. So, it hydrolyses its bound GTP to GDP, switching the signal off.

An oncogene is a mutated form of a normal cellular gene (the proto-oncogene) which codes for a protein which is either controlled abnormally so that it is expressed in abnormally large amounts or has gained activity so that it is more active than the normal protein.

Cancer is regarded as a genetic disease because it is caused by mutations in the genome. However, these mutations are normally in somatic cells, not germ cells and mutations contributing to cancer are rarely inherited. To form a malignant cancer, a cell must acquire a small number of mutations (probably about six) each of which gives the cell a growth or survival advantage.

Tumour suppressor genes code for proteins, which normally control progression through a cell cycle checkpoint. These genes only contribute to a cancer when both copies are mutated in a way which produces an inactive protein product. A single mutation inactivating only one gene has no effect. They contribute to cancer because the absence of the protein product removes controls on cell division.