In silico design of telomerase inhibitors

Bagiński, Maciej; Serbakowska, Katarzyna

doi:10.1016/j.drudis.2020.04.024

Cited by 11 publications

(6 citation statements)

References 56 publications

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“…TERT inhibition has been regarded as a promising therapeutic strategy, as earlier in vitro studies showed that TERT silencing cell proliferation ( 194 , 195 ). An early approach was to design compounds that would interact with DNA at the 3’ overhang, stabilizing telomeric G-quadruplex secondary structures, and thus blocking telomerase access to DNA.…”

Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

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Telomerase reverse transcriptase (TERT) is a catalytic subunit of telomerase. Telomerase complex plays a key role in cancer formation by telomere dependent or independent mechanisms. Telomere maintenance mechanisms include complex TERT changes such as gene amplifications, TERT structural variants, TERT promoter germline and somatic mutations, TERT epigenetic changes, and alternative lengthening of telomere. All of them are cancer specific at tissue histotype and at single cell level. TERT expression is regulated in tumors via multiple genetic and epigenetic alterations which affect telomerase activity. Telomerase activity via TERT expression has an impact on telomere length and can be a useful marker in diagnosis and prognosis of various cancers and a new therapy approach. In this review we want to highlight the main roles of TERT in different mechanisms of cancer development and regulation.

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Section: Tert As a Potential Therapeutic Targetmentioning

confidence: 99%

TERT—Regulation and Roles in Cancer Formation

et al. 2020

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“…24 They demonstrated through molecular docking that a benzodioxole derivative had potent telomerase inhibition alongside potent anticancer activity in human gastric and human melanoma cell lines. 25 This shows that this group may add additional benefit through telomerase inhibition in a different method of action to the one investigated here with G4 stabilisation. The 2,5-dimethylthiazole has been studied extensively in the form of the fluorescent marker thiazole orange for its intercalation potential.…”

Section: Rsc Medicinal Chemistrymentioning

confidence: 77%

Synthesis and evaluation of bis(imino)anthracene derivatives as G-quadruplex ligands

et al. 2021

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“…Gefitinib/erlotinib targeting EGFR mutations and crizotinib targeting ALK translocations have shown clinical benefit and approved for clinical use ( 23 ). telomerase reverse transcriptase (TERT) inhibition has been acted as a promising therapeutic strategy for LUAD ( 24 , 25 ). These mutated genes of LUAD may serve as potential targets, providing more possibilities and strategies for the treatment of LUAD.…”

Section: Discussionmentioning

confidence: 99%

Genomic Features of Organ-Specific Metastases in Lung Adenocarcinoma

Feng

et al. 2022

Front. Oncol.

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BackgroundThe genomic features of cancer cells may confer the metastatic ability of lung adenocarcinoma (LUAD) to metastasize to specific organs. We aimed to identify the differences in genomic alterations between patients with primary LUAD with and without metastases and to elucidate the metastatic biology that may help developing biomarker-directed therapies for advanced or metastatic disease.MethodsA retrospective cohort of 497 patients with LUAD including 388 primary tumors (PR), 53 bone metastases (MT-bone), 30 liver metastases (MT-liver), and 26 brain metastases (MT-brain) was tested for genomic alterations by a next-generation sequencing assay.ResultsThe EGFR, TP53, TERT, LRP1B, CDKN2A, ERBB2, ALK, and KMT2C genes had a high frequency of mutations, and the mutations were shared by PR and metastases groups. TP53 and EGFR were the most common mutated genes. In comparison with PR, KRAS, STK11, ATM, NPM1, and ROS1 were significantly mutated in MT-brain, and TP53, MYC, RSPO2, CDKN2a, and CDKN2B were significantly mutated in MT-liver. The frequencies of TP53, CDKN2A, MTAP, PRKCI, and APC mutations were higher in MT-bone than that in PR. The ERBB, phosphoinositide-3-kinase/protein kinase B (PI3K-AKT), cell cycle, Fibroblast growth factor (FGF), and homologous recombination deficiency signaling pathways were affected in both PR and metastases, and there is higher frequency of mutations in metastases. Moreover, the co-mutations in patients with PR and metastasis were respectively analyzed. In addition, the programmed death ligand 1 (PD-L1) level was obviously related to tumor stage and tumor metastases, and the tumor mutational burden was correlated to clinicopathological features including age, gender, pathological stages, and tumor metastases. FGFR1, KAT6A, MYC, RAD21, TP53, and DAXX were also dramatically correlated to the tumor mutational burden.ConclusionMetastases are the most devastating stage of tumors and the main cause of cancer-related deaths. Our results provided a clinically relevant view of the tumor-intrinsic mutational landscape of patients with metastatic LUAD.

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In silico design of telomerase inhibitors

Cited by 11 publications

References 56 publications

TERT—Regulation and Roles in Cancer Formation

TERT—Regulation and Roles in Cancer Formation

Synthesis and evaluation of bis(imino)anthracene derivatives as G-quadruplex ligands

Genomic Features of Organ-Specific Metastases in Lung Adenocarcinoma

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