Cell growth and maturation are normal events in organ development
during embryogenesis, growth, and tissue repair and remodeling after
injury. Disordered regulation of these processes can result in loss
of control over cell growth, differentiation, and spatial confinement.
Human neoplasia collectively represents a spectrum of diseases characterized
by abnormal growth and invasion of cells. Although cancers are typically classified
by their tissues of origin or anatomic location, many features are
shared by all types. There is also considerable variation among
patients with a given type of cancer in the nature of cellular alterations
as well as the clinical presentation and course of disease. The
recognition of overt malignancy by physical examination or imaging
requires the presence in the body of about 1 billion malignant cells.
A preclinical phase may sometimes be recognized. Preclinical
signs may consist of, among others, polyps in the colon or dysplastic
nevi on the skin—potential precursors of colon carcinoma
and malignant melanoma, respectively. Such precursor lesions usually
exhibit features of abnormal cell proliferation without the demonstration
of invasiveness and may precede the development of an invasive malignancy
by months to years, or may not progress to cancer within the individual’s
lifetime. More commonly, the preclinical phase goes undetected until
invasive cancer, occasionally with regional or distant metastases,
is already present. As is the case with other medical disorders,
our understanding of the pathophysiology of neoplasia has been based
on clinical and pathologic observations of large series of patients.
More recently, cellular and molecular features of cancer cells have
been described, and their relationships to certain neoplastic entities
and clinical situations have extended our knowledge in this field.
- 1. What is the preclinical phase of cancer?
- 2. How many malignant cells must be present
before overt signs of cancer are evident?
& Biochemical Basis of Neoplasia: Introduction
The process of neoplasia is a result of stepwise alterations
in cellular function. These phenotypic changes confer proliferative,
invasive, and metastatic potential that are the hallmarks of cancer.
It is generally believed—although not conclusively proved—that
genetic alterations underlie all cellular and biochemical aberrations
responsible for the malignant phenotype. In addition to mutational
changes that alter the genetic code, epigenetic changes also underlie
cellular and biochemical aberrations that contribute to the malignant
phenotype. Epigenetic phenomena influence gene expression and cell
behavior, and although once acquired they are transmitted to daughter
cells with cell division, they are not changes in the genetic code.
An example of this is the silencing of certain genes by hypermethylation
of DNA in the promoter region. An increasing number of genetic and
cellular changes are being catalogued from the study of cancer cells,
both in vivo, from primary tumors of patients, and in vitro, from
established cancer cell lines grown in tissue culture. Some alterations
are related to particular cellular phenotypes, such as a high proliferative
rate or metastatic potential. Some of these changes are specific