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Cited by 69Adrenal and Paraganglionic TumorsAdrenal Hormones and DisordersRenal cell carcinoma treatment

The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.

Ribonucleotide Reductase Large Subunit ( RRM1 ) Gene Expression May Predict Efficacy of Adjuvant Mitotane in Adrenocortical Cancer

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Volante, Marco, Terzolo, Massimo, Fassnacht, Martin, Rapa, Ida, Germano, Antonina, Sbiera, Silviu, Daffara, Fulvia, Sperone, Paola, Scagliotti, Giorgio, Allolio, Bruno, Papotti, Mauro, Berruti, Alfredo·2012·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-11-2692

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Abstract

PURPOSE: Mitotane is the most broadly used systemic therapy for adrenocortical carcinoma (ACC), but its mechanism of action and possible predictors of treatment response are currently poorly defined. Our aim was to evaluate the gene expression of ribonucleotide reductase large subunit 1 (RRM1) and excision repair cross-complementation group 1 (ERCC1) in ACC as potential biomarkers for clinical outcome and response to mitotane. EXPERIMENTAL DESIGN: Forty-five and 47 tissue samples from two cohorts (Orbassano, Italy; Wuerzburg, Germany) of completely resected ACC were centrally analyzed using real-time PCR for RRM1 and ERCC1 expression. Fifty-four patients received surgery alone and 38 received adjuvant mitotane after surgery. Clinical and pathologic features were highly comparable in the two series. H295R and SW-13 ACC cell lines were also used for pharmacologic tests. RESULTS: ERCC1 gene expression was not associated to clinical outcome. In contrast, high RRM1 gene expression was associated to shorter disease-free survival (DFS) and overall survival at both univariate and multivariate analysis. In patients with low RRM1 gene expression, adjuvant mitotane was associated with improved DFS, whereas this effect was lost in cases with high RMM1 expression. In vitro mitotane induced strong up regulation of RRM1 transcription (up to 25-fold increase) in mitotane-insensitive SW-13 but not in mitotane-sensitive H295R cells. Furthermore, RRM1 silencing in SW-13 cells induced sensitivity to mitotane. CONCLUSION: Our in vitro and in vivo data indicate that RRM1 gene expression is functionally associated to mitotane sensitivity and support a possible role of RRM1 determination as a novel molecular biomarker predicting response to adjuvant mitotane in ACC.

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Metadata

Authors
Volante, M., Terzolo, M., Fassnacht, M., Rapa, I., Germano, A., Sbiera, S., Daffara, F., Sperone, P., Scagliotti, G., Allolio, B., Papotti, M., & Berruti, A.
Affiliations
Universitätsklinikum Würzburg (DE)
Corresponding author
Berruti, Alfredo
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2012-06-14
Volume
18
Issue
12
Pages
3452-3461
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-11-2692
OpenAlex
W2114237399
Cited by
69
References
43
Citations by year
2026: 1 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 7
FWCI
7.17
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Associazione Italiana per la Ricerca sul Cancro (IG/10795/2010)
  • Deutsche Krebshilfe
  • Regione Piemonte
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
Keywords
adrenocortical carcinoma, mitotane, RRM1, ERCC1, adjuvant therapy, predictive biomarkers, treatment response, disease-free survival, overall survival, SW13 cells, H295R cells, gene expression
MeSH terms
Adolescent, Adrenal Cortex Neoplasms, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, DNA-Binding Proteins, Endonucleases, Female, Genetic Markers, Humans, Male, Middle Aged, Mitotane, Ribonucleoside Diphosphate Reductase, Biomarkers, Tumor, Treatment Outcome, Chemotherapy, Adjuvant, Disease-Free Survival, Tumor Suppressor Proteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Young Adult

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