TAILIEUCHUNG - Ebook A clinical approach to medicine (2E): Part 2
(BQ) Part 2 boook “A clinical approach to medicine” has contents: Medical oncology, neurology, pediatrics, obstetrics and gynecology, renal medicine, respiratory medicine, rehabilitative medicine, rheumatology. | Medical Oncology This page intentionally left blank 50 Pathogenesis of Cancer Richard Epstein GENERAL CONCEPTS Is cancer most accurately regarded as a disease, a group of different diseases, or a “normal” degenerative condition similar to aging? To gain insight into this key question, we need to consider what is already wellestablished about the natural history of human cancer. First, malignancy is remarkably uncommon in individuals younger than 40 years old, suggesting a Darwinian predilection for the postreproductive age group. Consistent with this, human cells are more difficult to transform in vitro than are cells of more short-lived mammalian species. Hence, genetic stability is an intrinsic property of cells which appears to vary inversely with cancer susceptibility in vivo. Second, tumor types which can be cured in their advanced stages tend to be rare, whereas common cancers in their advanced stages are usually incurable. This is not simply a matter of bad luck for the human race. Rather, it reflects the fact that rare neoplasms arise due to rare genetic events (which in turn are often flagged by characteristic chromosomal translocations), whereas common cancers arise via the progressive 869 870 A Clinical Approach to Medicine accumulation of common genetic mutations. This latter process results not only in loss of growth control, but also in profound genetic instability similar to that which normally confers an adaptive survival advantage on bacterial cells. Conversely, the sustained clinical remissions that famously accompany the treatment of certain advanced malignancies are likely to be related to the relatively normal composition (and hence stability) of the genome in those tumor cells. The main problem that most cancer patients face today is not rapid tumor cell growth as such, but rather the presence of genetic instability that transforms the disease into a therapeutic “moving target”. Not surprisingly, then, the distinction between rare and
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