Elsevier

Clinical Genitourinary Cancer

Volume 5, Issue 6, September 2007, Pages 379-385
Clinical Genitourinary Cancer

Original Contribution
Potential Histologic and Molecular Predictors of Response to Temsirolimus in Patients with Advanced Renal Cell Carcinoma

https://doi.org/10.3816/CGC.2007.n.020Get rights and content

Abstract

Purpose

Similar to other molecularly targeted agents, temsirolimus, an inhibitor of mammalian target of rapamycin, has shown promising activity in advanced renal cell carcinoma. However, only a subset of patients appears to derive significant tumor responses. In an effort to identify potential predictors of response to temsirolimus, tumor samples from a subset of patients within a randomized phase II trial of temsirolimus in advanced renal cell carcinoma were studied.

Patients and Methods

Paraffinembedded tissue sections from patients who had received temsirolimus were immunostained with antibodies to carbonic anhydrase IX, phospho- S6, phospho-Akt (pAkt), and phosphotase and tensin homologue. Expression levels were correlated with objective response (partial response [PR], minor response [MR]) and clinical benefit (PR, MR, SD ≤ 4 cycles) to temsirolimus. In addition, von Hippel–Lindau (VHL) mutational analysis was performed and correlated with response.

Results

Tissue specimens were obtained from 20 patients who were evaluable for both tumor response and staining for phospho-S6 and carbonic anhydrase IX. In addition, 19 specimens were evaluable for pAkt, and 18 for phosphotase and tensin homologue. VHL mutational analysis was performed on 16 samples. Five patients achieved an objective response (1 PR/4 MRs) to temsirolimus. There was a positive association of phospho-S6 expression (P = .02) and a trend toward positive expression of pAkt (P = .07) with response to temsirolimus. No patient without high expression of either phospho-S6 or pAkt experienced an objective tumor response. There was no correlation of carbonic anhydrase IX and phosphotase and tensin homologue expression or VHL status with response to temsirolimus.

Conclusion

These results suggest that phospho-S6 and pAkt expression are promising predictive biomarkers for response to temsirolimus that are worthy of further exploration for use in patient selection models for mammalian target of rapamycin inhibitors.

References (21)

There are more references available in the full text version of this article.

Cited by (161)

  • The emerging genetic landscape of renal cell carcinoma

    2023, Diagnostic Molecular Pathology: A Guide to Applied Molecular Testing, Second Edition
  • Mechanisms of resistance to mTOR inhibitors

    2020, Critical Reviews in Oncology/Hematology
View all citing articles on Scopus

Electronic forwarding or copying is a violation of US and International Copyright Laws.

Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1558-7673, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.

View full text