P53 STATUS AND THE EFFICACY OF CANCER-THERAPY IN-VIVO

The therapeutic responsiveness of genetically defined tumors expressin g or devoid of the p53 tumor suppressor gene was compared in immunocom promised mice. Tumors expressing the p53 gene contained a high proport ion of apoptotic cells and typically regressed after treatment with ga mma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptot ic cells. Acquired mutations in p53 were associated with both treatmen t resistance and relapse in p53-expressing tumors. These results estab lish that defects in apoptosis, here caused by the inactivation of p53 , can produce treatment-resistant tumors and suggest that p53 status m ay be an important determinant of tumor response to therapy.