Correspondence

Cancer Therapy Meets p53

N Engl J Med 1994; 331:1314-1315November 10, 1994

Article

To the Editor:

Kinzler and Vogelstein (July 7 issue)1 eloquently discuss the clinical implications of basic research on the p53 tumor-suppressor gene. In key statements, they suggest that p53 mutations may provide a genetic basis for drug resistance and that the relation between p53 mutations and therapeutic response should be verified. In fact, the field moves rapidly ahead, and a p53-dependent cross-resistance to ionizing radiation and chemotherapeutic agents can now be considered a well-established phenomenon. It occurs not only as a result of p53-dependent apoptosis modulating cytotoxicity,2 but also because of p53-dependent gene amplification,3 p53-dependent expression of the multidrug-resistance gene (MDR1),4 and p53-dependent cell proliferation.5-7

There is also strong evidence that p53-dependent cross-resistance is indeed clinically relevant, in that abnormal p53 negatively affects the prognosis of many tumors. Since the appearance in the Journal of the review article on p53 in 1993,5,6 additional data have been published on the predictive role of p53 mutations and the abnormal expression of p53 protein in a variety of tumors. Thus, p53-dependent cross-resistance is a complex phenomenon with a clear clinical importance.

H. Peter Rutz, M.D.
Basel University Hospital, CH-4031 Basel, Switzerland

7 References

1. 1

   Kinzler KW, Vogelstein B. Cancer therapy meets p53. N Engl J Med 1994;331:49-50
   Full Text | Web of Science | Medline

2. 2

   Lowe SW, Ruley HE, Jacks T, Housman DE. p53-Dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 1993;74:957-967
   CrossRef | Web of Science | Medline

3. 3

   Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell 1992;70:937-948
   CrossRef | Web of Science | Medline

4. 4

   Chin K-V, Ueda K, Pastan I, Gottesman MM. Modulation of activity of the promoter of the human MDR1 gene by Ras and p53. Science 1992;255:459-462
   CrossRef | Web of Science | Medline

5. 5

   Harris CC, Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318-1327
   Full Text | Web of Science | Medline

6. 6

   Clinical implications of the p53 tumor-suppressor geneN Engl J Med 1994;330:864-865
   Full Text | Web of Science | Medline

7. 7

   Bourhis J, Bosq J, Wilson GD, et al. Correlation between p53 gene expression and tumor-cell proliferation in oropharyngeal cancer. Int J Cancer 1994;57:458-462
   CrossRef | Web of Science | Medline

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