A heretical theory about the origins of cancer could explain a long-standing medical mystery - why cancers often become resistant to the drugs used to treat them.
The controversial theory, if correct, also suggests a possible way to treat cancer to restore its sensitivity to drugs.
The theory, espoused by Peter Duesberg, professor of molecular and cell biology in the College of Letters & Science at the University of California, Berkeley, disputes the common assumption that cancer results from a series of genetic mutations that kick a cell into uncontrolled growth.
Instead, Duesberg argues, cancer results from a wrench thrown into the machinery - the spindle apparatus - controlling chromosome splitting when a cell divides. This leads to an abnormal number of chromosomes that unbalances hundreds to thousands of genes and proteins in the cell and generates the many odd characteristics of cancer cells.
Cells with the wrong number of chromosomes are called aneuploid cells, and scientists have known for a long time that essentially all solid tumors are aneuploid. This was thought to be the result of the genetic mutations leading to cancer, however, not the cause of cancer.
One consequence of this aneuploidy is that the sensitive balance of proteins in the spindle apparatus also is upset, destabilizing the machinery that normally divides the chromosomes evenly between two daughter cells. As a result, each time a cell with an abnormal balance of chromosomes divides, it makes new mistakes in chromosome division, creating a snowball effect that keeps changing cellular properties, particularly in cancer cells with highly abnormal chromosome numbers.
In the Dec. 19, 2000, issue of the Proceedings of the National Academy of Sciences, Duesberg and his colleagues, UC Berkeley researcher Reinhard Stindl and Ruediger Hehlmann of the University of Heidelberg at Mannheim, Germany, reported the results of a simple experiment that bolsters their argument that
Contact: Robert Sanders
University of California - Berkeley