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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
TP53 mutations in advanced colorectal cancer: the dark side of the moon
Filippo Pietrantonio1, Pamela Biondani, Federica Perrone
1Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori (National Cancer Institute), Milan, Italy.
Background:
Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting.
Methods:
We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28).
Results:
Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes.
Conclusion:
TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.
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