The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study

Kandioler, Daniela; Schoppmann, Sebastian F.; Zwrtek, Ronald; Kappel, Sonja; Wolf, Brigitte; Mittlböck, Martina; Kührer, Irene; Hejna, Michael; Pluschnig, Ursula; Ba‐Ssalamah, Ahmed; Wrba, Fritz; Zacherl, Johannes

doi:10.1016/j.jtcvs.2014.06.079

Cited by 47 publications

(47 citation statements)

References 28 publications

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“…Both drugs are thought to depend on normal TP53 . The results of this study supported the hypothesis that TP53 could serve as potential predictive marker for response to neoadjuvant chemotherapy [7]. …”

Section: Introductionsupporting

confidence: 84%

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed—mutation rate of the marker higher than expected

et al. 2018

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SummaryBackgroundIn operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies.MethodBiomarker analysis was conducted using the mark53 analysis. Calculation of patient number needed was based on a 60% rate of marker positivity, deduced from the results of a phase II pilot study.ResultsFrom 2007–2012, the • Pancho trial recruited 235 patients with operable esophageal cancer in Austria. A total of 181 patients were eligible and could be subjected to mark53 analysis and randomization. After randomizing 74 patients, the overall TP53 mutation rate was 79%. However, due to the high prevalence of marker positivity, the number of projected patients was increased to 181 patients in order to ensure a sufficient number of marker-negative patients. After completion of the trial, the overall TP53 mutation rate was 77.9%.ConclusionDue to high medical need, the recruitment for the academic trial was excellent. Mark53 analysis clearly detected more mutations in the TP53 gene as compared to the cancer-specific p53 literature. Final analysis examining the interaction between the mark53 status and the effect of chemotherapies applied in the • Pancho trial is now awaited.

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Section: Introductionsupporting

confidence: 84%

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed—mutation rate of the marker higher than expected

et al. 2018

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“…For esophageal [4,6] and oropharyngeal cancer [7] and diffuse large B-cell lymphoma (DLBCL) [3], mutp53 was indeed a good predictor of resistance to chemotherapy. Cisplatin and fluorouracil were less efficacious in patients with esophageal and oropharyngeal cancer and the p53 mutations than in those with wild-type p53.…”

Section: The Role Of Mutp53 In Response To Clinical Chemotherapymentioning

confidence: 99%

“…Thus, p53 is a major candidate gene that can serve as a molecular marker in combination with other genes to be able to tailor chemotherapy to the individual patient. Recently, mutant p53 (mutp53) has been identified as a good predictor of chemoresistance in some clinical studies [3,4,5,6,7], and drugs targeting mutp53 have been developed. In this review, we provide an update regarding the mechanisms that underlie mutp53 gain of function (GOF) mutations, summarizing the mechanisms by which mutp53 induces chemoresistance and elucidating the role of mutp53 in clinical chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Mutant p53 Gain of Function and Chemoresistance: The Role of Mutant p53 in Response to Clinical Chemotherapy

Li²,

Guan³

et al. 2016

Chemotherapy

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Purpose: To review mechanisms underlying mutant p53 (mutp53) gain of function (GOF) and mutp53-induced chemoresistance, and to investigate the role of mutp53 in response to clinical chemotherapy. Methods: We searched the PubMed database for clinical studies from the past decade, including data evaluating the impact of mutp53 in clinical chemotherapy response. Results: Interactions between mutp53 and transcriptional factors, proteins or DNA structures, as well as epigenetic regulation, contribute to mutp53 GOF. Major mechanisms of mutp53-induced chemoresistance include enhanced drug efflux and metabolism, promoting survival, inhibiting apoptosis, upregulating DNA repair, suppressing autophagy, elevating microenvironmental resistance and inducing a stem-like phenotype. Clinically, mutp53 predicted resistance to chemotherapy in diffuse large B-cell lymphoma, and esophageal and oropharyngeal cancers, but its impact on chronic lymphocytic leukemia was unclear. In bladder cancer, mutp53 did not predict resistance, whereas in some breast and ovarian cancers, it was associated with sensitivity to certain chemotherapeutic agents. Conclusion: mutp53 has an intricate role in the response to clinical chemotherapy and should not be interpreted in isolation. Furthermore, when predicting tumor response to chemotherapy based on the p53 status, the drugs used should also be taken into consideration. These concepts require further investigation.

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“…A more recent study showed that EC patients with a normal TP53 status may benefit from nCRT with cisplatin/fluorouracil compared with mutant TP53 status (no immunohistochemical analysis performed). 47 Patients in our study were treated according to the CROSS regimen, consisting of carboplatin þ paclitaxel and radiotherapy. Carboplatin and radiotherapy are likely to act via a p53-controlled pathway, but docetaxel acts differently, and it is not clear if and how it interacts with TP53.…”

Section: Discussionmentioning

confidence: 99%

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy

et al. 2017

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The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study

Cited by 47 publications

References 28 publications

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed—mutation rate of the marker higher than expected

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed—mutation rate of the marker higher than expected

Mutant p53 Gain of Function and Chemoresistance: The Role of Mutant p53 in Response to Clinical Chemotherapy

P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy

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