Hypoxic Environment May Lead to Tumor Resistance

Hypoxic Environment May Lead to Tumor Resistance

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.

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