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14

The Nature of Living Things

14.5

Cancer

Cancer, nowadays the leading cause of mortality in many developed countries, is

defined as a disease involving a malignant tumour. A tumour is an abnormal lump

of tissue that apparently serves no physiological purpose; it is considered to be

malignant if it invades surrounding (normal) tissues or spreads to other parts of the

body (a process called metastasis).

Phenotypically, cancerous cells (i.e., those constituting a tumour) are character-

ized by rapid and undifferentiated proliferation. Practically, the only “differentiation”

that arises in a malignant tumour is angiogenesis, when the tumour is itself invaded by

blood vessels, which are very necessary to ensure its continued survival and growth.

Genotypically, the most characteristic feature of cancer is aneuploidy—an abnormal

number of chromosomes. Given that one of the most important factors determining

reproductive isolation and, hence, speciation is chromosome mismatch, malignant

tumours (cancers) may be considered to be foreign species within the host (i.e.,

having the status of parasites).

About 100 years ago, von Hanseman, and later Boveri, promulgated the view that

aneuploidy, itself triggered by unknown causes, was the cause of cancer. Later, the

idea that a few point mutations in certain genes were sufficient to upset the regulation

of the cell and cause cancer received intensive scrutiny, with the genetic correlates

assigned to certain stages in its progression (Table 14.3). Nevertheless, the “gene

mutation theory” has a number of weaknesses, notably ³⁶:

1. Many chemical carcinogens are not mutagens.

2. Presumed oncomutations cannot be detected in about 50% of cancers; conversely

cells carrying presumed oncomutations are often not cancerous.

3. Presumed oncomutations are heritable, but cancers are not.

4. The probability of being afflicted by cancer increases exponentially with age;

infants are essentially free of cancer; but the accumulation of the purportedly

required mutations during the lifetime of a human being implies unrealistically

high rates of mutation.

5. Exposure to some carcinogens results in cancer only after a very long (decades)

period of latency (so-called neoplastic latency).

Cell division (mitosis), especially in eukaryotes, is an intricate affair. According

to the “chromosomal theory” of cancer, carcinogens are aneuploidogens that upset

the delicate and complex molecular machinery of mitosis, ³⁷ resulting in cell division

with the chromosomes unequally distributed between the two daughter cells. This

results in massive genotypic aberration, equivalent to thousands of point mutations

occurring in a very short time. Although many such cells are simply not viable,

presumably a few survive—indeed one may be sufficient—and form the beginning

of a cancer. The abnormal karyotype appears to confer extraordinary genotypic and

phenotypic instability, such that the cancer continues to evolve, developing more

36 See Duesberg et al. (2005).

37 For example, they could bind to some of the proteins, changing their affinities to the others.