Abstract
P53 mutations are associated with invasive tumors in mouse models. We assessed the p53 mutations and survival in patients with advanced cancer treated in the Phase I Program. Of 691 tested patients, 273 (39.5%) had p53 mutations. Patients with p53 mutations were older (p<.0001) and had higher numbers of liver metastases (p=.005). P53 mutations were associated with higher numbers of other aberrations; PTEN (p=.0005) and HER2 (p=.003) aberrations were more common in the p53 mutation group. No survival difference was observed between patients with p53 mutations and those with wild-type p53. In patients with wild-type p53 and other aberrations, patients treated with matched-therapy against the additional aberrations had longer survival compared to those treated with non-matched-therapy or those who received no therapy (median survival, 26.0 vs. 11.8 vs. 9.8 months, respectively; p=.0007). Results were confirmed in a multivariate analysis (p=.0002). In the p53 mutation group with additional aberrations, those who received matched-therapy against the additional aberrations had survival similar to those treated with non-matched-therapy or those who received no therapy (p=.15). In conclusion, our results demonstrated resistance to matched-targeted therapy to the other aberrations in patients with p53 mutations and emphasize the need to overcome this resistance.
Original language | English (US) |
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Pages (from-to) | 3871-3879 |
Number of pages | 9 |
Journal | Oncotarget |
Volume | 5 |
Issue number | 11 |
DOIs | |
State | Published - 2014 |
Keywords
- Matched therapy
- Molecular aberrations
- P53 mutations
ASJC Scopus subject areas
- Oncology
MD Anderson CCSG core facilities
- Biostatistics Resource Group
- Clinical Trials Office