PALO ALTO, Calif--New research into the nature of malignant cells
deep within the interior of solid tumors suggests a possible explanation
as to why tumors with large hypoxic areas tend to be aggressive
and treatment resistant.
The research team, led by Dr. Amato J. Giaccia of Stanford University,
studied the central area of tumors where the blood supply is poor,
causing hypoxia. Their work in a murine model showed that the
hypoxic state stimulates production of the p53 protein, which
can block cell proliferation or lead to cell self-destruction.
While large numbers of malignant cells in the tumor interior die
in this way, some tumor cells in the hypoxic environment acquire
a p53 gene mutation that prevents their destruction and allows
them to survive with little oxygen, giving them a distinct competitive
advantage in the hypoxic environment over cells that lack the
gene defect, Dr. Giaccia says (Nature, January 4, 1996).
Such tumor cells may be resistant to chemotherapy and radiation,
since, thanks to the p53 mutation, they are no longer affected
by the treatment-induced DNA damage that stimulates production
of p53, says Dr. Giaccia and his colleagues at Stanford, MIT,
the University of Pennsylvania, and Cold Spring Harbor Laboratory.
These resistant cells can eventually take over the entire tumor,
producing an aggressive malignancy that is resistant from the
time of diagnosis.