Telomere length is a novel predictive biomarker of sensitivity to anti-EGFR therapy in metastatic colorectal cancer
Open accessAbstract
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.
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Augustine et al. demonstrated in vitro that shorter telomere length correlated with restricted growth in response to cetuximab, while patients with longer telomere length exhibited a longer progression-free survival when treated with EGFR inhibitors (cetuximab/panitumumab).
“Augustine et al. demonstrated in vitro that shorter TL correlated with restricted growth in response to cetuximab (an anti-EGFR antibody), while patients with longer TL exhibited a longer PFS when treated with EGFR inhibitors (cetuximab/panitumumab) [220].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [220]
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Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy
Nikolouzakis, T. K., Chrysos, E., Docea, A. O., Fragkiadaki, P., Souglakos, J., Tsiaoussis, J., & Tsatsakis, A. (2024) · Cancers · doi:10.3390/cancers16111995 · Cited by 37 · see citing works
Telomeres and telomerase in the clinical management of colorectal cancer
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- Authors
- Augustine, T. A., Baig, M., Sood, A., Budagov, T., Atzmon, G., Mariadason, J. M., Aparo, S., Maitra, R., & Goel, S.
- Affiliations
- Albert Einstein College of Medicine (US)
- Montefiore Medical Center (US)
- Ludwig Cancer Research (AU)
- Corresponding author
- Goel, S
- Venue
- British Journal of Cancer
- Published
- 2014-11-20
- Volume
- 112
- Issue
- 2
- Pages
- 313-318
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC4453445
- OpenAlex
- W2073965780
- Cited by
- 27
- References
- 30
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 3
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- Funders
- American Society of Clinical Oncology
- National Institutes of Health (1k12ca132783-01a1)
- National Cancer Institute (K12-CA132783, 1K12CA132783-01A1, P30CA013330)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Keywords
- telomere length, metastatic colorectal cancer, anti-EGFR therapy, cetuximab, predictive biomarkers, EGFR signaling, telomerase, KRAS wild-type, progression-free survival, drug sensitivity
- MeSH terms
- Cetuximab, Panitumumab, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Agents, Female, Humans, Liver Neoplasms, Male, Middle Aged, Biomarkers, Tumor, Colorectal Neoplasms, Telomere, Disease-Free Survival, Drug Resistance, Neoplasm, Cell Line, Tumor, Molecular Targeted Therapy, Telomere Shortening, Antibodies, Monoclonal, Humanized, ErbB Receptors
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