Matches in SemOpenAlex for { <https://semopenalex.org/work/W2054285616> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W2054285616 abstract "Invasive breast cancer (IBC) is a heterogeneous disease with distinct molecular and histological features as well as diverse biological behaviors. It is thus critical to find specific gene aberrations that can drive breast cancer initiation and progression as potential therapeutic targets. Our lab has established bioinformatics workflows to identify therapeutic oncogene targets. We have nominated Tousled-Like Kinase 2 (TLK2) as a candidate therapeutic target from 44,932 human genes based on integrative copy number data from The Cancer Genome Atlas (TCGA). TLK2 is a nuclear serine/threonine kinase that serves as a cell cycle checkpoint regulating chromosome assembly, and is inactivated by phosphorylation through the ATM dependent manner in the response to the double strand breaks during the S-phase. Interestingly, we observed 12–14% of focal TLK2 gene amplifications and translocations in invasive breast cancers, which are more frequent in luminal B tumors. Chromosomal aberrations may leads the deregulation of TLK2 kinase activity and results in overcoming the cell cycle checkpoint upon DNA damage such as IR or chemotherapeutic drugs treatments in breast cancer, thus destabilizing the cancer genome. Indeed, our preliminary data show that TLK2 knockdown substantially inhibits cell proliferation in breast cancer cells overexpressing TLK2. Further, this response is sustained in their derivative strains resistant to hormone or anti-Her2 therapies, suggesting the potential of TLK2 inhibition to sensitize these therapies as well. Overall, I expect that this study will provide compelling evidence regarding the role of TLK2 in breast cancer tumorigenesis and genomic instability, and establish its potential as a therapeutic target. The possibility of developing specific TLK2 inhibitors can be well demonstrated by the previous success of drugs against other cell cycle checkpoint kinases that are currently under clinical trials. In addition, molecular assays detecting TLK2 derangements may be applied in the clinics to identify patients who might benefit from future TLK2 inhibitor. If TLK2 endows resistance or sensitivity to other therapies, assays detecting TLK2 aberrations may also have important predictive value for personalization of these treatments. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD09-08." @default.
- W2054285616 created "2016-06-24" @default.
- W2054285616 creator A5030115311 @default.
- W2054285616 creator A5043122883 @default.
- W2054285616 creator A5074102383 @default.
- W2054285616 creator A5077747866 @default.
- W2054285616 creator A5079325383 @default.
- W2054285616 date "2012-12-15" @default.
- W2054285616 modified "2023-09-27" @default.
- W2054285616 title "Abstract PD09-08: The potential role of TLK2 as a therapeutic target in breast cancer." @default.
- W2054285616 doi "https://doi.org/10.1158/0008-5472.sabcs12-pd09-08" @default.
- W2054285616 hasPublicationYear "2012" @default.
- W2054285616 type Work @default.
- W2054285616 sameAs 2054285616 @default.
- W2054285616 citedByCount "0" @default.
- W2054285616 crossrefType "proceedings-article" @default.
- W2054285616 hasAuthorship W2054285616A5030115311 @default.
- W2054285616 hasAuthorship W2054285616A5043122883 @default.
- W2054285616 hasAuthorship W2054285616A5074102383 @default.
- W2054285616 hasAuthorship W2054285616A5077747866 @default.
- W2054285616 hasAuthorship W2054285616A5079325383 @default.
- W2054285616 hasConcept C104317684 @default.
- W2054285616 hasConcept C121608353 @default.
- W2054285616 hasConcept C140752955 @default.
- W2054285616 hasConcept C143425029 @default.
- W2054285616 hasConcept C154137905 @default.
- W2054285616 hasConcept C173396325 @default.
- W2054285616 hasConcept C178169997 @default.
- W2054285616 hasConcept C2781018059 @default.
- W2054285616 hasConcept C29537977 @default.
- W2054285616 hasConcept C30481170 @default.
- W2054285616 hasConcept C502942594 @default.
- W2054285616 hasConcept C530470458 @default.
- W2054285616 hasConcept C54355233 @default.
- W2054285616 hasConcept C552990157 @default.
- W2054285616 hasConcept C555283112 @default.
- W2054285616 hasConcept C60644358 @default.
- W2054285616 hasConcept C62478195 @default.
- W2054285616 hasConcept C86554907 @default.
- W2054285616 hasConcept C86803240 @default.
- W2054285616 hasConcept C88216763 @default.
- W2054285616 hasConceptScore W2054285616C104317684 @default.
- W2054285616 hasConceptScore W2054285616C121608353 @default.
- W2054285616 hasConceptScore W2054285616C140752955 @default.
- W2054285616 hasConceptScore W2054285616C143425029 @default.
- W2054285616 hasConceptScore W2054285616C154137905 @default.
- W2054285616 hasConceptScore W2054285616C173396325 @default.
- W2054285616 hasConceptScore W2054285616C178169997 @default.
- W2054285616 hasConceptScore W2054285616C2781018059 @default.
- W2054285616 hasConceptScore W2054285616C29537977 @default.
- W2054285616 hasConceptScore W2054285616C30481170 @default.
- W2054285616 hasConceptScore W2054285616C502942594 @default.
- W2054285616 hasConceptScore W2054285616C530470458 @default.
- W2054285616 hasConceptScore W2054285616C54355233 @default.
- W2054285616 hasConceptScore W2054285616C552990157 @default.
- W2054285616 hasConceptScore W2054285616C555283112 @default.
- W2054285616 hasConceptScore W2054285616C60644358 @default.
- W2054285616 hasConceptScore W2054285616C62478195 @default.
- W2054285616 hasConceptScore W2054285616C86554907 @default.
- W2054285616 hasConceptScore W2054285616C86803240 @default.
- W2054285616 hasConceptScore W2054285616C88216763 @default.
- W2054285616 hasLocation W20542856161 @default.
- W2054285616 hasOpenAccess W2054285616 @default.
- W2054285616 hasPrimaryLocation W20542856161 @default.
- W2054285616 hasRelatedWork W1513728748 @default.
- W2054285616 hasRelatedWork W2001033586 @default.
- W2054285616 hasRelatedWork W2017941025 @default.
- W2054285616 hasRelatedWork W2049275490 @default.
- W2054285616 hasRelatedWork W2082390970 @default.
- W2054285616 hasRelatedWork W2291124025 @default.
- W2054285616 hasRelatedWork W2332288585 @default.
- W2054285616 hasRelatedWork W2401546034 @default.
- W2054285616 hasRelatedWork W2755230067 @default.
- W2054285616 hasRelatedWork W2775183538 @default.
- W2054285616 hasRelatedWork W2788877376 @default.
- W2054285616 hasRelatedWork W2790251171 @default.
- W2054285616 hasRelatedWork W2883670730 @default.
- W2054285616 hasRelatedWork W2887054120 @default.
- W2054285616 hasRelatedWork W2887784392 @default.
- W2054285616 hasRelatedWork W2890390417 @default.
- W2054285616 hasRelatedWork W3009108765 @default.
- W2054285616 hasRelatedWork W3016055296 @default.
- W2054285616 hasRelatedWork W3186561161 @default.
- W2054285616 hasRelatedWork W2292007526 @default.
- W2054285616 isParatext "false" @default.
- W2054285616 isRetracted "false" @default.
- W2054285616 magId "2054285616" @default.
- W2054285616 workType "article" @default.