title: Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Augustine
authors.affiliation: Department of Medicine/Division of Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY 10461, USA.
authors.forename: M
authors.initials: M
authors.lastname: Baig
authors.affiliation: Department of Medicine/Division of Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY 10461, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sood
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: T
authors.initials: T
authors.lastname: Budagov
authors.affiliation: Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: G
authors.initials: G
authors.lastname: Atzmon
authors.affiliation: Department of Medical Oncology, Ludwig Institute for Cancer Research, 145-163 Studley Road, Heidelberg, VIC 3084, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Mariadason
authors.affiliation: 1] Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA [2] Department of Medicine/Division of Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY 10461, USA.
authors.forename: S
authors.initials: S
authors.lastname: Aparo
authors.affiliation: Department of Medicine/Division of Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY 10461, USA.
authors.forename: R
authors.initials: R
authors.lastname: Maitra
authors.affiliation: 1] Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA [2] Department of Medicine/Division of Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY 10461, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D045744:Cell Line, Tumor; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D000077544:Panitumumab; D016615:Telomere; D059506:Telomere Shortening
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab