Abstract
Length of the telomere (TL), a structure at the tip of chromosome that protects and ensures stability, is determined by multi-protein complexes such as telosome/shelterin and telomerase. Earlier studies from our laboratory show that longer TL has potential to be positive predictive biomarker of clinical outcome to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy in patients with KRAS WT metastatic colorectal cancer. Although there is extensive literature suggesting the role of shelterin and telomerase, not much literature exists that describes the role of EGFR and KRAS pathway in regulating TL. This detailed review focuses on an insight into various components, including proteins, enzymes and transcription factors, interlinking between EGFR pathways and telomerase that regulate TL.
Highlights
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States when men and women are considered separately, and the second leading cause when both sexes are combined[1, 2]
A small subset of about 1–2% of CRC cases arises as a consequence of inflammatory bowel diseases. ∼84% of sporadic CRC has genetic instability characterized by chromosomal instability (CIN), whereas as ∼13–16% has hypermutation and show microsatellite instability [4] due to defective DNA mismatch repair (MMR), often associated with wild-type tumor protein p53 (TP53) and a near-diploid pattern of CIN
We reported that TL has potential to be a novel and unique predictive biomarker of clinical outcome to anti-epidermal growth factor receptor (EGFR) therapy in patients with KRAS www.impactjournals.com/Genes&Cancer type (WT) metastatic CRC
Summary
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States when men and women are considered separately, and the second leading cause when both sexes are combined[1, 2]. EGF stimulation via EGFR pathways, mainly RAS/RAF/MAPK, PI3K/AKT/MTOR, JAK/STAT and direct activation of transcription factors ETS-2, MYC, MAD and MAX, help to interact with TERT in order to elongate telomeres. Www.impactjournals.com/Genes&Cancer using clinical studies, we and others have demonstrated that mutations in the PI3K/AKT/mTOR signaling pathway predict for resistance to cetuximab[18, 19].
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