Basic principles of the molecular biology of cancer I

Although many different types of cancer exist, similar mechanisms may underlie their development. Cancers occur when cells escape the mechanisms that control cell growth, and proliferate in an uncontrolled fashion, acquiring the ability to invade surrounding tissues and metastasize to distant sites. Malignant cells are genetically unstable, and possess several mutations, each of which overcomes a natural anti-cancer defence. These mutations continue to occur even after tumour development, which causes difficulties in finding treatments for cancers. Genes related to cancer development may be divided into oncogenes (which act to increase cell proliferation, and which are upregulated in malignancy) and tumour suppressor genes (which inhibit cell growth, and are downregulated in cancers). The abnormal activity of oncogenes and tumour suppressor genes may promote tumour growth in a number of ways. They may result in the production of stimulatory growth signals via alterations in extracellular growth factors or their receptors, or by alterations in intracellular signalling pathways. Important intracellular signalling molecules are often coded for by oncogenes, such as ras or myc. For example, ras is mutated in many human cancers. Another way in which cancer cells can proliferate abnormally is by resistance to normal inhibitory growth signals, or resistance to apoptosis. An example is the tumour suppressor p53, which normally acts to prevent damaged cells from dividing, and whose function is lost in many types of cancer. A combination of different genetic alterations is present within tumours, with the result that the normal balance between cell division and cell death is lost.