The Biology of Cancer - Vibrational Spectroscopy for Tissue Analysis - page 37

the appearance of the neoplasm. This latency phenomenon or tumour induc-
tion time occurs even when the carcinogen is administered continuously to
an experimental animal [3]. This is probably because of the fact that can-
cer develops through a succession of stages marked by the accumulation of
genetic events within the cell [18].
It is generally believed that most cancers have a monoclonal (single-cell)
origin [18]. This single cell can give rise to a focus of neoplastic cells. In
the case of epithelial tissues, if the neoplastic cells are confined to the epi-
thelium, the lesion is regarded as a precancer. These precancer lesions can
progress by invading the basement membrane to become full cancers [1,3].
It has been recognized that gross changes in genetic material, particularly
nonrandom chromosomal abnormalities such as translocations, character-
ize many human cancers [9]. These abnormalities are illustrated by dividing
excessively to form lumps and tumours and also by failing to differentiate
normally [3]. The progression from normal cell to cancer cell is a complex
multistep process, which is called carcinogenesis .
Carcinogenesis is a multistep process involving the cooperation of several
oncogenic mutations [20-23]. Single oncogenic mutations are not sufficient to
cause malignancy, as they frequently induce multiple contradictory signals
inhibiting cancer cell proliferation [24]. This is exemplified in the control of
cell cycle progression, where activation of signals can stimulate or inhibit
cell cycle entry [25,26]. In this context, cell cycle inhibition often results from
a stress response mediated by activation of the tumour suppressors (such as
p. 53), which is disabled upon loss of function of these genes, leading to stim-
ulation of uncontrolled proliferation [27-29].
Initially, genetic alterations are thought to confer a growth advantage to
individual cells by either decreasing tumour suppressor gene activity or
increasing oncogene activity or both. Further genetic alterations result in the
development of cell clones that have the ability to invade adjacent tissues,
establish metastatic deposits, and evade immune surveillance. At some point
in the process, these malignant cell clones also lose the normal ability to
respond to hormonal growth regulatory signatures [11]. Cell changes con-
tinue to occur even after a cancer has formed [5].
In a simple description of carcinogenesis, a tumour (or neoplasm) begins
when some cell within a normal population sustains a mutation that increases
its propensity to proliferate ( tumour initiation ) [7]. The altered cell and its
daughters look normal, but they grow and divide too much. This condition
is termed hyperplasia . After some time, which can be years, one of these cells
suffers another mutation that further reduces control on cell growth. This cell
proliferates very fast and the offspring of this cell appears abnormal in shape
and orientation. This state is known as dysplasia . Again, after some time, a
mutation occurs that alters cell behavior ( tumour progression ) [7]. The affected
cells become even more abnormal in growth and appearance. If the tumour
is contained within original tissue, it is called in-situ carcinoma . If cells break
away from such a tumour, they can travel through the bloodstream or lymph