Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer

T. A. Augustine, M. Baig, A. Sood, T. Budagov, G. Atzmon, J. M. Mariadason, S. Aparo, R. Maitra, S. Goel

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Background: Telomeres are TTAGGG tandem repeats capping chromosomal ends and partially controlled by the telomerase enzyme. The EGFR pathway putatively regulates telomerase function, prompting an investigation of telomere length (TL) and its association with anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). Methods: Colorectal cancer cell lines were treated with multiple drugs and sensitivity determined. Clinical information was gathered from 75 patients who had received anti-EGFR drugs. Telomere length was measured using a validated qRT-PCR technique. Results: In CRC cell lines, TL independently predicted cetuximab sensitivity. Cells with shorter TL had growth inhibition of 18.6± 3.41% as compared with 41.39±8.58% in longer TL (P = 0.02). These in vitro findings were validated clinically, in a robust multivariate model. Among patients with KRas WT tumours, those with longer TL had a superior median progression-free survival (PFS) of 24.9 weeks than those with shorter TL; median 11.1 weeks, HR 0.31; P = 0.048. Conclusion: Telomere length could be a potential unique biomarker predictive of clinical benefit (PFS) of mCRC patients treated with anti-EGFR therapy. This is the novel demonstration of a complex hitherto undescribed interaction, placing anti-EGFR therapy, EGFR pathway, and the telomerase complex within a clinical context.

Original languageEnglish (US)
Pages (from-to)313-318
Number of pages6
JournalBritish Journal of Cancer
Volume112
Issue number2
DOIs
StatePublished - Jan 20 2015

Keywords

  • Cetuximab
  • Epidermal growth factor receptor (EGFR)
  • Metastatic colorectal cancer
  • Panitumumab
  • Predictive biomarker
  • Telomere length

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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