Original Article

Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro†

  1. Claudio Festuccia1,*,
  2. Giovanni Luca Gravina1,2,
  3. Leda Biordi3,
  4. Sandra D'Ascenzo4,
  5. Vincenza Dolo4,
  6. Corrado Ficorella5,
  7. Enrico Ricevuto5,
  8. Vincenzo Tombolini1,2

Article first published online: 26 JUN 2009

DOI: 10.1002/pros.20995

Issue

The Prostate

The Prostate

Volume 69, Issue 14, pages 1529–1537, 1 October 2009

Additional Information

How to Cite

Festuccia, C., Gravina, G. L., Biordi, L., D'Ascenzo, S., Dolo, V., Ficorella, C., Ricevuto, E. and Tombolini, V. (2009), Effects of EGFR tyrosine kinase inhibitor erlotinib in prostate cancer cells in vitro. The Prostate, 69: 1529–1537. doi: 10.1002/pros.20995

Author Information

  1. 1

    Laboratory of Radiobiology, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

  2. 2

    Division of Radiotherapy, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

  3. 3

    Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

  4. 4

    Department of Scienza della Salute, University of L'Aquila, L'Aquila, Italy

  5. 5

    Division of Oncology, Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy

*Laboratory of Radiobiology, Department of Experimental Medicine, Via Vetoio, Coppito-2, 67100 L'Aquila, Italy.

  1. †

    Claudio Festuccia and Giovanni Luca Gravina contributed equally to this work.

Publication History

  1. Issue published online: 24 AUG 2009
  2. Article first published online: 26 JUN 2009
  3. Manuscript Accepted: 13 MAY 2009
  4. Manuscript Received: 4 MAR 2009

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Keywords:

  • EGFR;
  • prostate cancer;
  • erlotinib

Abstract

BACKGROUND

Erlotinib is a small-molecule tyrosine kinase inhibitor targeted EGFR, known to be overexpressed in a variety of cancers, including prostate cancer. Clinical trials showed insignificant clinical benefit in patients with castration resistant prostate cancer both when EGFR inhibitors were administered as monotherapy or in association with antiandrogens or chemotherapeutics. Why, differently to other tumors, have EGFR inhibitors been so ineffective in human prostate cancer? This is the question that we have set in this report.

METHODS

For this purpose, the effectiveness of erlotinib, a selective EGFR inhibitor, in a wide range of prostate cancer cells (wild type or engineered to overexpress peculiar proteins including androgen receptor and PTEN).

RESULTS

We demonstrated that the effectiveness of erlotinib was inversely correlated to the EGFR/Her2 ratio rather than EGFR/p-EGFR or Her2/p-Her2 levels. Chronic treatment with bicalutamide induced overexpression of Her2 and reduction of EGFR/Her2ratio and this was associated with increased Akt and Erk activity. In these conditions of treatment a reduced efficacy of erlotinib was observed. At the same time, an increased efficacy versus erlotinib was documented in cancer cells chronically exposed to DHT. In these culture conditions low levels of Her2 and increased EGFR/Her2 ratio were evidenced.

CONCLUSIONS

Taken together, our results seem to suggest that a low EGFR/Her2 ratio and PTEN absence are the main factors responsible of erlotinib inefficacy. Therefore the inhibition of EGFR could have important antitumor effects in hormone-naive rather than in hormonally treated patients. Prostate 69: 1529–1537, 2009. © 2009 Wiley-Liss, Inc.

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