Oncotarget

Research Papers:

Characteristics and survival of patients with advanced cancer and p53 mutations

Rabih Said, Yang Ye, David S. Hong, Filip Janku, Siqing Fu, Aung Naing, Jennifer J. Wheler, Razelle Kurzrock, Christoforos Thomas, Gary A. Palmer, Kenneth R. Hess, Kenneth Aldape and Apostolia M. Tsimberidou _

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Oncotarget. 2014; 5:3871-3879. https://doi.org/10.18632/oncotarget.2004

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Abstract

Rabih Said1,2, Yang Ye1, David S. Hong1, Filip Janku1, Siqing Fu1, Aung Naing1, Jennifer J. Wheler1, Razelle Kurzrock1,3, Christoforos Thomas4, Gary A. Palmer5, Kenneth R. Hess6, Kenneth Aldape7 and Apostolia M. Tsimberidou1

1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX

2 Department of Internal Medicine, Oncology Division, The University of Texas Health Sciences Center, Houston, TX

3 Center for Personalized Therapy and Clinical Trials, University of California San Diego - Moores Cancer Center, San Diego, CA

4 Department of Biology and Biochemistry, University of Houston, Houston, Texas

5 Foundation Medicine, Cambridge, MA

6 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX

7 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

Correspondence:

Apostolia-Maria Tsimberidou, email:

Keywords: p53 mutations, matched therapy, molecular aberrations

Received: February 21, 2014 Accepted: May 23, 2014 Published: May 25, 2014

Abstract

P53 mutations are associated with invasive tumors in mouse models. We assessed the p53mutations 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.


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