ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
The Role of the TP53 Pathway in Predicting Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- MET-amplified gastric cancers exhibit co-amplifications of BRAF, CDK6, and EGFR.The journal of pathology. Clinical research · 2026Article
- JAK2 and NOTCH2 in gastric cancer - NOTCH2 is an independent prognosticator of poor patient outcome.Virchows Archiv : an international journal of pathology · 2026Article
- MDM2-amplified esophageal adenocarcinomas exhibit an activated metabolic and immunosuppressive phenotype with multiple potential therapeutic targets.BMC cancer · 2025Article
- Mutations in CREBBP and EP300 HAT and Bromo Domains Drive Hypermutation and Predict Survival in GI Cancers Treated with Immunotherapy.Biomedicines · 2025Article
- Artificial neural networks as a prognostic tool using hyperspectral imaging on pretherapeutic histopathological specimens of esophageal adenocarcinoma.Journal of cancer research and clinical oncology · 2025Article
- TP53-centric ctDNA complements PET/CT for non-invasive assessment of pathological complete response and survival after neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma: a prospective cohort study.International journal of surgery (London, England) · 2025Observational
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
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- Detection of a NovelGenes · 2023Article
- P53 Deficiency Accelerates Esophageal Epithelium Intestinal Metaplasia Malignancy.Biomedicines · 2023Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
purposeIn patients with locally advanced esophageal adenocarcinoma, response to neoadjuvant therapy strongly predicts survival, but robust molecular predictors of response have been lacking. We therefore sought to discover meaningful predictors of response in these patients. EXPERIMENTAL
designWe retrospectively identified all patients with adenocarcinoma of the lower esophagus or gastroesophageal junction who (i) were treated with multimodality therapy with curative intent at our institution from 2014 through 2020 and (ii) underwent prospective sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Clinicopathologic and genomic data were analyzed to identify potential genomic features, somatic alterations, and oncogenic pathways associated with treatment response.
resultsIn total, 237 patients were included. MDM2 amplification was independently associated with poor response to neoadjuvant therapy [OR, 0.10 (95% confidence interval, 0.01-0.55); P = 0.032], when accounting for significant clinicopathologic variables, including clinical stage, tumor grade, and chemotherapy regimen. Moreover, TP53 pathway alterations, grouped according to inferred severity of TP53 dysfunction, were significantly associated with response to neoadjuvant therapy (P = 0.004, q = 0.07). Patients with MDM2 amplifications or truncating biallelic TP53 mutations had similar outcomes in terms of poor responses to neoadjuvant therapy and, consequently, shorter progression-free survival, compared with patients with TP53 pathway wild-type tumors. Thus, worsening TP53 dysfunction was directly correlated with worse outcomes.
conclusionsMDM2 amplification and TP53 status are associated with response to therapy in patients with esophageal adenocarcinoma. Given the dearth of actionable targets in esophageal adenocarcinoma, MDM2 inhibition, in combination with cytotoxic chemotherapy, may represent an important therapeutic strategy to overcome treatment resistance and improve outcomes in these patients.
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