Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

Berg, Remco M. van den; Brokx, Hes A.; Vesin, Aurélien; Field, John K.; Brambilla, Christian; Meijer, Chris J.L.M.; Sutedja, G.; Heideman, Daniëlle A.M.; Postmus, Pieter E.; Smit, Egbert F.; Snijders, Peter J.F.

doi:10.3892/ijo_00000694

Int J Oncol

2010

DOI: 10.3892/ijo_00000694

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Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

Remco M. van den Berg

Hes A. Brokx

Aurélien Vesin

et al.

Abstract: Abstract. Lung cancer is the most important cause of cancerrelated mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification.

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Cited by 5 publications

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Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer

Chen,

Vallega,

Wang

et al. 2024

Journal of Experimental Medicine

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The inevitable acquired resistance to osimertinib (AZD9291), an FDA-approved third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR activating or T790M resistant mutations, limits its long-term clinical benefit. Telomere maintenance via telomerase reactivation is linked to uncontrolled cell growth and is a cancer hallmark and an attractive cancer therapeutic target. Our effort toward understanding the action mechanisms, including resistance mechanisms, of osimertinib has led to the identification of a novel and critical role in maintaining c-Myc–dependent downregulation of hTERT, a catalytic subunit of telomerase, and subsequent inhibition of telomerase/telomere and induction of telomere dysfunction in mediating therapeutic efficacy of osimertinib. Consequently, osimertinib combined with the telomere inhibitor, 6-Thio-dG, which is currently tested in a phase II trial, effectively inhibited the growth of osimertinib-resistant tumors, regressed EGFRm NSCLC patient-derived xenografts, and delayed the emergence of acquired resistance to osimertinib, warranting clinical validation of this strategy to manage osimertinib acquired resistance.

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Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer

Chen,

Vallega,

Wang

et al. 2024

Journal of Experimental Medicine

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The prognostic significance of hTERT overexpression in cancers

Wang¹,

Wang²,

Liu³

et al. 2018

Medicine

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Telomerase regulation and the intimate relationship with aging

Morgan¹

2013

RRBC

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Advancing age in humans is associated with a decline in function of physiological systems, as well as the onset and progression of many chronic diseases. An ongoing focus of basic aging research is to identify biomarkers that could be used to assess the severity of age-related diseases or that could also be modulated to treat them. Telomerase is an enzyme with mechanistic links to telomere length homeostasis and cell viability. Human telomerase is a ribonucleoprotein complex that consists of its catalytic subunit (hTERT) and ribonucleic acid template (hTERC). Telomerase adds de novo TTAGGG repeats to the ends of telomeres, which may prevent telomere shortening and subsequent dysfunction in certain cell compartments. Telomerase function within the cell represents a growing area of interest among biologists who study human aging, due to its potential use as a biomarker and therapeutic target for chronic disease. Here I review the basic biology of telomerase and the consequences of telomerase overexpression and deficiency in human cells and animal models. I discuss the putative role of telomerase in telomere-length homeostasis with advancing age in humans. Finally, I describe novel nontelomeric activities of telomerase related to cell viability and mitochondrial function.

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Prognostic value of hTERT mRNA expression in surgical samples of lung cancer patients: the European Early Lung Cancer Project

Abstract: Abstract. Lung cancer is the most important cause of cancerrelated mortality. Resectability and eligibility for treatment with adjuvant chemotherapy is determined by staging according to the TNM classification.

Cited by 5 publications

References 38 publications

Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer

Inhibition of hTERT/telomerase/telomere mediates therapeutic efficacy of osimertinib in EGFR mutant lung cancer

The prognostic significance of hTERT overexpression in cancers

Telomerase regulation and the intimate relationship with aging

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