4.7 Review

Telomerase: A prominent oncological target for development of chemotherapeutic agents

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Review Oncology

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.

CANCER DISCOVERY (2022)

Article Chemistry, Medicinal

In Silico Design, Synthesis, and Biological Evaluation of Anticancer Arylsulfonamide Endowed with Anti-Telomerase Activity

Giulia Culletta et al.

Summary: Telomerase plays an important role in tumor progression and is a potential target for developing cancer therapeutics. In this study, a structure-based approach was used to design potential inhibitors of telomerase. Compound 2C showed promising activity against the K-562 cell line and demonstrated better selectivity compared to a known inhibitor. Further optimization of the structure of compound 2C is warranted to obtain more active telomerase inhibitors.

PHARMACEUTICALS (2022)

Article Biochemistry & Molecular Biology

CRISPR/Cas: A New Tool in the Research of Telomeres and Telomerase as Well as a Novel Form of Cancer Therapy

Mahendar Porika et al.

Summary: Telomeres and telomerase play a crucial role in senescence, aging, and disease. The advancement of CRISPR-related technologies allows targeted genetic studies to modify genes associated with telomeres and telomerase, leading to a better understanding of cancer development and aging mechanisms.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Multidisciplinary Sciences

Structure of active human telomerase with telomere shelterin protein TPP1

Baocheng Liu et al.

Summary: This study reveals the structure of human telomerase and its interaction with TPP1. The binding of TPP1 to TERT activates telomerase activity. Additionally, the study found that elements in TERT and TER involved in template and telomeric DNA handling are structurally similar to those in Tetrahymena telomerase, providing unique insights into the mechanism of telomerase activity.

NATURE (2022)

Article Multidisciplinary Sciences

Structural basis of human telomerase recruitment by TPP1-POT1

Zala Sekne et al.

Summary: This study presents the structures of DNA-bound telomerase in complex with TPP1 and TPP1-POT1, revealing crucial interactions for telomerase recruitment to telomeres and providing a framework for future mechanistic work on telomerase regulation.

SCIENCE (2022)

Article Multidisciplinary Sciences

TGS1 mediates 2,2,7-trimethyl guanosine capping of the human telomerase RNA to direct telomerase dependent telomere maintenance

Valentina Buemi et al.

Summary: Researchers have found that the trimethylguanosine capping of the RNA component of the human telomerase complex plays an important role in directing telomere maintenance and suppressing the ALT pathway in cancer cells.

NATURE COMMUNICATIONS (2022)

Article Chemistry, Multidisciplinary

Facile induction and stabilization of intramolecular antiparallel G-quadruplex of d(TTAGGG)n on interaction with triazine-2-imidazole ethyl amine compound and its Cu(II), Zn(II) complexes under no-salt conditions

Renuga Duraisamy et al.

Summary: The synthesis of three compounds, trizImEA, Cu-trizImEA, and Zn-trizImEA, was carried out and their binding capacity with different DNA structures was elucidated. CD measurements showed that Cu-trizImEA and Zn-trizImEA stabilize the G-quadruplex of HTelo(8) and HTelo(20), and induce and stabilize the antiparallel G-quadruplex conformation of d(TTAGGG)(n) under no salt conditions. The compounds exhibited strong binding and effectively stabilized G-quadruplex structures.

JOURNAL OF CHEMICAL SCIENCES (2022)

Article Biochemistry & Molecular Biology

Synthesis, telomerase inhibitory and anticancer activity of new 2-phenyl-4H-chromone derivatives containing 1,3,4-oxadiazole moiety

Xu Han et al.

Summary: The study synthesized 66 2-phenyl-4H-chromone derivatives with potential telomerase inhibitory activity, with compound A33 showing significant inhibition. A33 was found to arrest cell cycle at G2/M phase and induce apoptosis in a concentration-dependent manner, while also reducing dyskerin expression.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2021)

Review Oncology

Making a Cold Tumor Hot: The Role of Vaccines in the Treatment of Glioblastoma

Stephen C. Frederico et al.

Summary: The use of immunotherapies for brain tumors has generated excitement, but challenges remain in treating GBM due to its immunologically cold nature. Strategies such as vaccine therapy combined with immune checkpoint inhibitors are being explored to overcome these challenges and enhance treatment options for patients with GBM in the future.

FRONTIERS IN ONCOLOGY (2021)

Review Immunology

Telomerase as a Target for Therapeutic Cancer Vaccines and Considerations for Optimizing Their Clinical Potential

Espen Basmo Ellingsen et al.

Summary: Telomerase-based therapeutic cancer vaccines have shown potential in clinical research and may enhance the efficacy of checkpoint inhibition. With its almost universal presence in cancer and essential role in tumor growth, telomerase is an attractive therapeutic target. Rational treatment combinations, such as checkpoint inhibitors, are likely necessary to fully unlock the clinical potential of telomerase-based cancer vaccines.

FRONTIERS IN IMMUNOLOGY (2021)

Article Oncology

Phase 1 study of safety, tolerability and immunogenicity of the human telomerase (hTERT)-encoded DNA plasmids INO-1400 and INO-1401 with or without IL-12 DNA plasmid INO-9012 in adult patients with solid tumors

Robert H. Vonderheide et al.

Summary: In this clinical trial, plasmid DNA-encoded hTERT/IL-12 DNA immunotherapy was well-tolerated, immune responses were noted across all tumor types, and a specific CD8+ phenotype increased by the immunotherapy was significantly correlated with survival in patients with pancreatic cancer.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

Article Biochemistry & Molecular Biology

Targeted Covalent Inhibition of Telomerase

Rick C. Betori et al.

ACS CHEMICAL BIOLOGY (2020)

Review Pharmacology & Pharmacy

In silico design of telomerase inhibitors

Maciej Baginski et al.

DRUG DISCOVERY TODAY (2020)

Review Oncology

Telomeres and telomerase in oncogenesis

Tomasz Trybek et al.

ONCOLOGY LETTERS (2020)

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The powerful world of antisense oligonucleotides: From bench to bedside

Anais M. Quemener et al.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2020)

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Shalini Bajaj et al.

MEDICINAL RESEARCH REVIEWS (2020)

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Anti-Cancer Immunotherapies Targeting Telomerase

Simone Negrini et al.

CANCERS (2020)

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Molecular principles of metastasis: a hallmark of cancer revisited

Jawad Fares et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Compromised Chondrocyte Differentiation Capacity in TERC Knockout Mouse Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer

Wei-Fang Chang et al.

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Epigallocatechin-3-gallate induces telomere shortening and clastogenic damage in glioblastoma cells

Ion Udroiu et al.

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Telomerase-Targeted Cancer Immunotherapy

Eishiro Mizukoshi et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Article Biochemistry & Molecular Biology

Targeted and Persistent 8-Oxoguanine Base Damage at Telomeres Promotes Telomere Loss and Crisis

Elise Fouquerel et al.

MOLECULAR CELL (2019)

Article Biochemistry & Molecular Biology

A non-natural nucleotide uses a specific pocket to selectively inhibit telomerase activity

Wilnelly Hernandez-Sanchez et al.

PLOS BIOLOGY (2019)

Review Oncology

Cancer overdiagnosis: a biological challenge and clinical dilemma

Sudhir Srivastava et al.

NATURE REVIEWS CANCER (2019)

Review Biochemistry & Molecular Biology

Telomerase Inhibitors from Natural Products and Their Anticancer Potential

Kumar Ganesan et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

Article Chemistry, Medicinal

Targeting G-quadruplex DNA structures in the telomere and oncogene Promoter regions by benzimidazole-carbazole ligands

Mangesh H. Kaulage et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2018)

Review Genetics & Heredity

Correlation between telomerase and mTOR pathway in cancer stem cells

Fatma Dogan et al.

Article Biochemistry & Molecular Biology

Telomerase Inhibition by a New Synthetic Derivative of the Aporphine Alkaloid Boldine

Sakineh Kazemi Noureini et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

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Implications of TERT promoter mutations and telomerase activity in urothelial carcinogenesis

Cagatay Guenes et al.

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Leukocyte Telomere Length and Pancreatic Cancer Risk: Updated Epidemiologic Review

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NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer

Andrew T. Ludlow et al.

NATURE COMMUNICATIONS (2018)

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Immunotherapy in Glioblastoma

Jessica A. Wilcox et al.

WORLD NEUROSURGERY (2018)

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Natural killer cells and other innate lymphoid cells in cancer

Laura Chiossone et al.

NATURE REVIEWS IMMUNOLOGY (2018)

Article Biochemistry & Molecular Biology

Pot1 OB-fold mutations unleash telomere instability to initiate tumorigenesis

P. Gu et al.

ONCOGENE (2017)

Review Cell Biology

Telomere-driven diseases and telomere-targeting therapies

Paula Martinez et al.

JOURNAL OF CELL BIOLOGY (2017)

Review Biochemistry & Molecular Biology

The Hammerhead Ribozyme: A Long History for a Short RNA

Marcos de la Pena et al.

MOLECULES (2017)

Review Immunology

Telomerase based anticancer immunotherapy and vaccines approaches

Chahal Kailashiya et al.

VACCINE (2017)

Review Cell Biology

Telomere Biology-Insights into an Intriguing Phenomenon

Shriram Venkatesan et al.

Review Biochemistry & Molecular Biology

Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide-Oligonucleotide Conjugates

Maria Taskova et al.

CHEMBIOCHEM (2017)

Review Biochemistry & Molecular Biology

Treating Cancer by Targeting Telomeres and Telomerase

Marko Ivancich et al.

ANTIOXIDANTS (2017)

Article Biochemistry & Molecular Biology

Widespread telomere instability in prostatic lesions

LiRen Tu et al.

MOLECULAR CARCINOGENESIS (2016)

Article Chemistry, Medicinal

Identification of human telomerase inhibitors having the core of N-acyl-4,5-dihydropyrazole with anticancer effects

Xuan Xiao et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2016)

Review Oncology

Long Noncoding RNAs in Cancer Pathways

Adam M. Schmitt et al.

CANCER CELL (2016)

Review Chemistry, Medicinal

Telomerase as a Cancer Target. Development of New Molecules

D. L. Mengual Gomez et al.

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2016)

Review Chemistry, Medicinal

Telomerase inhibitors: a patent review (2010-2015)

Ruo-Jun Man et al.

EXPERT OPINION ON THERAPEUTIC PATENTS (2016)

Article Chemistry, Organic

Telomerase Inhibitors: Potential Anticancer Agents

Rakesh R. Somani et al.

MINI-REVIEWS IN ORGANIC CHEMISTRY (2016)

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Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies

Mohammad A. Jafri et al.

GENOME MEDICINE (2016)

Review Genetics & Heredity

Therapeutic Targeting of Telomerase

Kathrin Jaeger et al.

Review Genetics & Heredity

Telomere and Telomerase Therapeutics in Cancer

Yucheng Xu et al.

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Telomerase: a target for colorectal cancer treatment?

Elias Kouroumalis

CELL CYCLE (2015)

Article Biochemistry & Molecular Biology

Boldine, a natural aporphine alkaloid, inhibits telomerase at non-toxic concentrations

Sakineh Kazemi Noureini et al.

CHEMICO-BIOLOGICAL INTERACTIONS (2015)

Article Chemistry, Medicinal

Novel myricetin derivatives: Design, synthesis and anticancer activity

Wei Xue et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2015)

Article Chemistry, Medicinal

Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: Synthesis and anticancer activity

Jing Bo Shi et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2015)

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Beginning at the end: DNA replication within the telomere

Susan A. Gerbi

JOURNAL OF CELL BIOLOGY (2015)

Article Genetics & Heredity

DCAF4, a novel gene associated with leucocyte telomere length

Massimo Mangino et al.

JOURNAL OF MEDICAL GENETICS (2015)

Article Biochemistry & Molecular Biology

Structural Basis of Telomerase Inhibition by the Highly Specific BIBR1532

Christopher Bryan et al.

STRUCTURE (2015)

Article Oncology

Perifosine as a potential novel anti-telomerase therapy

Brody Holohan et al.

ONCOTARGET (2015)

Article Biotechnology & Applied Microbiology

Immunogenicity of GX301 cancer vaccine: Four (telomerase peptides) are better than one

Daniela Fenoglio et al.

HUMAN VACCINES & IMMUNOTHERAPEUTICS (2015)

Article Dentistry, Oral Surgery & Medicine

Telomerase activity in the occurrence and progression of oral squamous cell carcinoma

Yuji Miyazaki et al.

JOURNAL OF ORAL SCIENCE (2015)

Article Chemistry, Multidisciplinary

Synthesis of novel, azasugar-modified anthraquinone derivatives and their cytotoxicity

Ping-Zhu Zhang et al.

CHINESE CHEMICAL LETTERS (2014)

Editorial Material Genetics & Heredity

Mutations in POT1 predispose to familial cutaneous malignant melanoma

L. Trigueros-Motos

CLINICAL GENETICS (2014)

Article Biochemistry & Molecular Biology

Telomerase structure

Sara Sandin et al.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2014)

Article Biochemistry & Molecular Biology

Progress in structural studies of telomerase

Edward J. Miracco et al.

CURRENT OPINION IN STRUCTURAL BIOLOGY (2014)

Article Chemistry, Medicinal

Telomere Maintenance as a Target for Drug Discovery

Vijay Sekaran et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

Article Biochemistry & Molecular Biology

Targeting DNA-PKcs and telomerase in brain tumour cells

Resham Lal Gurung et al.

MOLECULAR CANCER (2014)

Review Gastroenterology & Hepatology

Telomere and telomerase in chronic liver disease and hepatocarcinoma

Lucia Carulli et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2014)

Review Biochemistry & Molecular Biology

Natural products: A continuing source of novel drug leads

Gordon M. Cragg et al.

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS (2013)

Article Chemistry, Medicinal

Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors

Yin Luo et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2013)

Review Oncology

Novel anticancer therapeutics targeting telomerase

Maria Ruden et al.

CANCER TREATMENT REVIEWS (2013)

Article Biochemistry & Molecular Biology

Inhibition of Telomerase Recruitment and Cancer Cell Death

Mai Nakashima et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2013)

Article Biochemistry & Molecular Biology

Curcumin inhibits telomerase and induces telomere shortening and apoptosis in brain tumour cells

Aik Kia Khaw et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2013)

Article Chemistry, Organic

Total Synthesis of Dictyodendrins B and E

Jingjing Liang et al.

JOURNAL OF ORGANIC CHEMISTRY (2013)

Article Medicine, General & Internal

Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine

Daniel D. Von Hoff et al.

NEW ENGLAND JOURNAL OF MEDICINE (2013)

Article Multidisciplinary Sciences

Highly Recurrent TERT Promoter Mutations in Human Melanoma

Franklin W. Huang et al.

SCIENCE (2013)

Review Biochemistry & Molecular Biology

Telomerase: central regulator of all of the hallmarks of cancer

Kee Chung Low et al.

TRENDS IN BIOCHEMICAL SCIENCES (2013)

Review Biotechnology & Applied Microbiology

Clinical implications of antitelomeric drugs with respect to the nontelomeric functions of telomerase in cancer

Jae-il Roh et al.

ONCOTARGETS AND THERAPY (2013)

Article Biochemistry & Molecular Biology

Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation

G-H Ha et al.

CELL DEATH AND DIFFERENTIATION (2012)

Review Pharmacology & Pharmacy

G-Quadruplex Binding Ligands: from Naturally Occurring to Rationally Designed Molecules

Tuong Vy Thi Le et al.

CURRENT PHARMACEUTICAL DESIGN (2012)

Review Oncology

hTERT-based therapy: A universal anticancer approach (Review)

Mu-Han Lu et al.

ONCOLOGY REPORTS (2012)

Review Oncology

Recent Patents on Anti-Telomerase Cancer Therapy

Apurva Agrawal et al.

RECENT PATENTS ON ANTI-CANCER DRUG DISCOVERY (2012)

Article Chemistry, Medicinal

Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents

Xin-Hua Liu et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2011)

Review Biochemistry & Molecular Biology

Hallmarks of Cancer: The Next Generation

Douglas Hanahan et al.

Review Chemistry, Multidisciplinary

Chemistry in human telomere biology: structure, function and targeting of telomere DNA/RNA

Yan Xu

CHEMICAL SOCIETY REVIEWS (2011)

Editorial Material Nursing

Revisiting the Hallmarks of Midwifery

Frances E. Likis

JOURNAL OF MIDWIFERY & WOMENS HEALTH (2010)

Article Biochemistry & Molecular Biology

Telomeres and Telomerase: From Discovery to Clinical Trials

David R. Corey

CHEMISTRY & BIOLOGY (2009)

Article Pharmacology & Pharmacy

Cancer vaccination with telomerase peptide GV1001

Jon Amund Kyte

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2009)

Review Hematology

Telomere maintenance and human bone marrow failure

Rodrigo T. Calado et al.

Article Oncology

Immunogenicity of the hTERT540-548 peptide in cancer

Lynn Wenandy et al.

CLINICAL CANCER RESEARCH (2008)

Review Oncology

Telomerase and cancer therapeutics

Calvin B. Harley

NATURE REVIEWS CANCER (2008)

Article Pharmacology & Pharmacy

A new steroid derivative stabilizes g-quadruplexes and induces telomere uncapping in human tumor cells

Bertrand Brassart et al.

MOLECULAR PHARMACOLOGY (2007)

Article Pharmacology & Pharmacy

Mechanism of acridine-based telomerase inhibition and telomere shortening

Mekala Gunaratnam et al.

BIOCHEMICAL PHARMACOLOGY (2007)

Article Chemistry, Multidisciplinary

Core-shell and segmented polymer-metal composite nanostructures

Michal Lahav et al.

NANO LETTERS (2006)

Article Cell Biology

Potent inhibition of human telomerase by U-73122

Yi-Jui Chen et al.

JOURNAL OF BIOMEDICAL SCIENCE (2006)

Article Chemistry, Organic

Total synthesis of (R)-telomestatin

Takayuki Doi et al.

ORGANIC LETTERS (2006)

Review Oncology

Telomeres and telomerase as targets for anticancer drug development

KA Olaussen et al.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2006)

Review Oncology

The telomeric PARP, tankyrases, as targets for cancer therapy

H Seimiya

BRITISH JOURNAL OF CANCER (2006)

Article Biotechnology & Applied Microbiology

Development and characterization of a monoclonal antibody directed against human telomerase reverse transcriptase (hTERT)

D Soldateschi et al.

JOURNAL OF BIOTECHNOLOGY (2005)

Review Genetics & Heredity

Telomeres and human disease: Ageing, cancer and beyond

MA Blasco

NATURE REVIEWS GENETICS (2005)

Article Biotechnology & Applied Microbiology

Function, replication and structure of the mammalian telomere

D Broccoli

CYTOTECHNOLOGY (2004)

Article Biochemistry & Molecular Biology

Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate

E Pascolo et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

Article Biochemistry & Molecular Biology

A highly selective telomerase inhibitor limiting human cancer cell proliferation

K Damm et al.

EMBO JOURNAL (2001)

Article Pharmacology & Pharmacy

Interaction of deoxyguanosine nucleotide analogs with human telomerase

SW Tendian et al.

MOLECULAR PHARMACOLOGY (2000)

Review Pharmacology & Pharmacy

G-quadruplex DNA: a potential target for anti-cancer drug design

HY Han et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2000)