p53 Status and the Efficacy of Cancer Therapy in Vivo

Abstract

The therapeutic responsiveness of genetically defined tumors expressing or devoid of the p53 tumor suppressor gene was compared in immunocompromised mice. Tumors expressing the p53 gene contained a high proportion of apoptotic cells and typically regressed after treatment with gamma radiation or adriamycin. In contrast, p53-deficient tumors treated with the same regimens continued to enlarge and contained few apoptotic cells. Acquired mutations in p53 were associated with both treatment resistance and relapse in p53-expressing tumors. These results establish that defects in apoptosis, here caused by the inactivation of p53, can produce treatment-resistant tumors and suggest that p53 status may be an important determinant of tumor response to therapy.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…In point of fact, a number of studies raise the possibility that cells lacking p53 activity might more readily survive certain forms of cancer therapy (Lowe et al, 1994).…”

Expression of Bcl-2 in node-negative breast cancer is associated with various prognostic factors, but does not predict response to one course of perioperative chemotherapy

“…Recently, evidence has been obtained that wild-type as well as most mutant p53 proteins can down-regulate Bcl-2 expression in vitro and in vivo (Haldar et al, 1994;Selvakumaran et al, 1994;. Mutations in the p53 tumour-suppressor gene are a marker of poor prognosis in node-negative breast cancer (Isola et al, 1992) and experimental data have demonstrated increased resistance to doxorubicin and gamma irradiation in tumours lacking functional p53 (Lowe et al, 1994). We also evaluated the predictive value of Bcl-2 expression on responsiveness in the subgroup of patients with p53-negative tumours.…”

Methylation-induced silencing of ASC and the effect of expressed ASC on p53-mediated chemosensitivity in colorectal cancer

“…Several clinical and experimental trials have shown the inactivation of p53 to be correlated with resistance to chemotherapy in colorectal cancers (Lowe et al, 1994;Bunz et al, 1999). p53 is a transcriptional factor, which induces its target genes, such as p21, Bax, Noxa, and Puma, to regulate either cell cycle arrest or apoptosis in response to chemotherapeutic drugs (el-Deiry et al, 1993;Miyashita and Reed, 1995;Vogelstein et al, 2000;Oda et al, 2000;Yu et al, 2003).…”