Abstract
During the last few decades, cancer research has focused on the idea that cancer is caused by genetic alterations and that this disease can be treated by reversing or targeting these alterations. The small variations in cancer mortality observed during the previous 30 years indicate, however, that the clinical applications of this approach have been very limited so far. The development of future gene-based therapies that may have a major impact on cancer mortality may be compromised by the high number and variability of genetic alterations recently found in human tumors. This article reviews evidence that tumor cells, in addition to acquiring a complex array of genetic changes, develop an alteration in the metabolism of oxygen. Although both changes play an essential role in carcinogenesis, the altered oxygen metabolism of cancer cells is not subject to the high genetic variability of tumors and may therefore be a more reliable target for cancer therapy. The utility of this novel approach for the development of therapies that selectively target tumor cells is discussed.
Highlights
The genetic basis of cancer was discovered more than a century ago, when David von Hansemann observed that cells from various carcinoma samples had chromosomal alterations
We are beginning to realize that the high genetic variability of tumor cells is a serious obstacle for the design of genebased therapies that may have a major impact on cancer mortality [12,21]
In addition to building up a complex array of genetic changes, tumor cells acquire an alteration in the metabolism of oxygen, a process that plays an important role in carcinogenesis and could be exploited to develop therapies for a broad range of patients with cancer
Summary
The genetic basis of cancer was discovered more than a century ago, when David von Hansemann observed that cells from various carcinoma samples had chromosomal alterations. Epigenetic alterations (heritable and reversible changes other than the DNA sequence) and aneuploidy (numerical and structural abnormalities in chromosomes) are common alterations in tumor cells, which modify gene expression and may play a crucial role in carcinogenesis [14,15,16,17,18] Such is the genetic complexity and variability of tumor cells, that the REVIEW ARTICLE idea of understanding cancer in terms of changes in specific genes is losing ground in favor of proposals that seek to rationalize cancer in terms of a limited number of acquired phenotypes (the so-called hallmarks of cancer) and altered cellular pathways [19,20,21]. In addition to building up a complex array of genetic changes, tumor cells acquire an alteration in the metabolism of oxygen, a process that plays an important role in carcinogenesis and could be exploited to develop therapies for a broad range of patients with cancer
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