cancer

cancer The term ‘cancer’ refers to a diverse group of diseases, characterized by uncontrolled growth of cells, leading to a variety of pathological consequences and frequently death. It is typically a disease of the elderly — the incidence of all forms of cancer increases markedly with age. However, it also occurs occasionally in children. Often the abnormal cell growth results in the establishment of a macroscopic lump or tumour ‘oncos’ in Greek, hence the term ‘oncology’ for the study of cancer), which may grow to a large size and kill the patient by a local effect, e.g. occlusion of vital ducts — even the alimentary tract — or by compromising the functioning of some distant organ. Indeed, the very word ‘cancer’ derives from the appearance of solid tumours as noted on post mortem examination by early physicians, who likened their appearance to that of a crab (Cancer) because of the irregular and disorganized appearance of the threads of the tumour radiating from a central body. Some forms of cancer, however, do not grow as coherent lumps but as individual cells diffused through the vascular system; these diseases — leukaemias and lymphomas — are associated with quite a different pathological profile.

Not all tumours of the human body are cancerous, however. Everyone is familiar with the common wart, and probably other skin lesions that result from local proliferation of cells, and which are quite benign. What distinguishes cancerous tumours and renders them seriously life-threatening is the property of malignancy, which derives from the capacity of the cells to invade surrounding tissue and to break off from the parent lump, migrate around the body in the blood vessels or the lymphatic system, and set up secondary foci of cancerous growth at distant sites. It is the latter phenomenon, metastatic spread of the disease, which most frequently kills cancer patients. The secondary foci — metastases — often occur in the brain, lungs, or liver, because these organs have a large blood supply and a well-developed capillary bed of tiny vessels in which single cancer cells or clumps of cells can lodge. By contrast, many common skin cancers (with the singular exception of malignant melanoma) are invasive but not metastatic, so they can be cured by simple excision of the tumour together with a decent margin of surrounding tissue. This emphasizes the seriousness of metastasis in the pathology of cancer. It is also salutary that in many instances cancer patients present with clear evidence of metastatic disease, such as secondary tumours radiologically visible in the lung, but no sign of the primary lump. It may take all the skill of an experienced histopathologist to indicate the probable origin of the diseased cells, knowledge of which is likely to be crucial for any form of clinical management.

Cancer therapy involves four modalities which may be employed singly or in combination: surgery, radiotheraphy, chemotherapy, or a group of less well-defined treatments, of which immunotherapy is the chief example. It is common practice to employ surgery where applicable (to reduce the tumour burden if a single large mass has been detected e.g. by X-rays or magnetic resonance imaging), followed by localized or whole-body radiotherapy to attack residual disease, and/or chemotherapy to deal with distant metastases. If the disease is advanced, with obvious metastasis, chemotherapy with a cocktail of three or four powerfully cytotoxic drugs may be the only worthwhile option. Most of these drugs are DNA-reactive chemicals which directly attack the genetic blueprints of the rogue cells. Alternatively a massive dose of whole-body irradiation may be attempted, and the patient rescued from death due to destruction of his bone marrow by subsequent reimplantation of his own marrow cells, collected prior to treatment and ‘cleaned up’ in vitro (autologous bone marrow transplantation).

Cancer is increasingly seen as a lifestyle disease, caused at least partly by environmental influences, with important modulation by the genetic inheritance of the individual. Sometimes viral infections may start the process off. In other cases sunlight is to blame, particularly in causing skin cancers among fair-skinned Caucasians living in tropical countries or under the ozone hole of the Southern hemisphere. Sometimes it is diet which seems to trigger disease, especially of the gastrointestinal tract: here fats are held suspect, and a high-fibre diet rich in cereals and vegetables is to be recommended. But far and away the most serious, and preventable, environmental cause of cancer is tobacco smoking, which is inexorably linked to cancer of the lung. On this conclusion the epidemiological evidence is stark — witness the sharp continuing rise in lung cancer among women in the Western world, which correlates precisely with the changes in social attitudes to smoking over the last 50 years.

One of the hottest areas of cancer research by the end of the twentieth century was the identification of genes that impart an inherited susceptibility to cancer of particular organs, or to cancer in general. Early successes have been the discovery of BRCA1 and BRCA2, genes which predispose to breast cancer — still the most common form of malignancy in Western women — and there are more to come. Other cancer-prone individuals carry genes whose products are enzymes known to be intimately associated with the biological phenomena of cell signalling, gene transcription, or DNA repair. A picture is beginning to emerge of cancer development, starting with a single cell exposed to some external influence, which causes a mutation in one of a small number of critical genes, ‘initiating’ the process of escape from growth control. Other genetic changes, leading to aneuploidy (abnormalities in the nature or the number of chromosomes), follow over a period which may be as long as several years, while so-called ‘promoter’ substances exacerbate the multiplication of the abnormal cells into a small tumour, which begins to invade its surroundings and may start to metastasise. In the later stages of disease the cells enter a ‘progression’ phase, in which gross rearrangements of their genetic make-up occur — these, can be seen down the microscope as wholesale redistribution of chromosomes, involving deletions, translocations, breaks, duplications, and doubtless many more subtle changes. Genetic instability can proceed to a state of chromosomal chaos — a ‘point of no return’ whereby cells cannot revert to the normal karyotype (the characteristics of its chromosomes) and must be killed. At that stage the disease is rampant and only the most aggressive intervention, including treatment with drugs which have dire toxic side-effects, is likely to produce any relief or remission, and cure is most unlikely. Often the side-effects (hair loss, vomiting and diarrhoea, neurological disorders, or bone marrow suppression) are so serious as to be unacceptable to the sick patient, and palliative treatment with powerful opiates is all that can be recommended. The most recent scientific findings emphasize the importance in tumour control of programmed cell death (apoptosis) and shortening of the far end, of the ‘arms’ of chromosomes (the telomeres) during replication. Chemotherapeutic and radiotherapeutic strategies induce apoptosis, so escape from programmed death signals is important.

M. J. Waring

See also chemotherapy; radiotherapy.