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Last update 08 May 2025

Ku70/80

Last update 08 May 2025

Basic Info

Synonyms-

Introduction-

Drugs associated with Ku70/80

VIO-01

Target

Ku70/80 x MRN x PARP1

Mechanism

Ku70/80 inhibitors [+2]

Active Org.-

Originator Org.

Valerio Therapeutics SA

Active Indication-

Inactive Indication

HRR Gene-mutated Castration-Resistant Prostate Cancer [+4]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with Ku70/80

NCT06257758

/ TerminatedPhase 1/2

A Phase 1/2 Study of VIO-01 in Participants With Recurrent Solid Tumors

The goal of this phase 1/2 clinical trial is to investigate the safety of an investigational drug called VIO-01 when taken by people who have different types of solid tumor cancers. There are two parts to this trial, part 1 and part 2.
Part 1 of the trial aims to answer these questions:
* The safety and tolerability of VIO-01 when it is given alone or in combination with other anti-cancer therapies.
* The highest dose that people can take without having unacceptable side effects
* How well your body tolerates the drug alone or in combination, how they are absorbed, and the effects they have on your disease.
Part 2 of the trial will further test VIO-01's effect in participants with advanced HRRm or HRD+ solid tumors and HRRm/HRD+ recurrent ovarian cancer.
Participants will follow a schedule of visits to the study site to have assessments done related to their health condition and to receive the trial treatment.

Start Date10 Jan 2024

Sponsor / Collaborator

Valerio Therapeutics SA

100 Clinical Results associated with Ku70/80

100 Translational Medicine associated with Ku70/80

0 Patents (Medical) associated with Ku70/80

315

Literatures (Medical) associated with Ku70/80

01 Jun 2025·Molecular Therapy Nucleic Acids

High-throughput 3D spheroid screens identify microRNA sensitizers for improved thermoradiotherapy in locally advanced cancers

Article

Author: Snoek, Barbara C ; Steenbergen, Renske D M ; Martinovičová, Dominika ; van de Wiel, Mark A ; Huseinovic, Angelina ; Oei, Arlene L ; Xu, MengFei ; van Beusechem, Victor W ; Stalpers, Lukas J A

Chemoradiotherapy is the standard of care for many locally advanced cancers, including cervical and head and neck cancers, but many patients cannot tolerate chemotherapy. Clinical trials have shown that radiotherapy combined with hyperthermia (thermoradiotherapy) may be equally effective, yet it yields a suboptimal overall survival of patients, emphasizing the need for improvement. MicroRNAs (miRNAs), short non-coding RNA sequences, are often dysregulated in cancer and exhibit significant potential as radiosensitizers by targeting genes associated with the DNA damage response. In this study, high-throughput miRNA screening of four cervical cancer cell lines identified 55 miRNAs with significant sensitizing potential, with 18 validated across 10 additional cancer cell lines (6 cervical and 4 head and neck). Functional studies of 6 miRNAs, including miR-16, miR-27a, miR-181c, miR-221, miR-224, and miR-1293, showed that they reduced DNA damage repair by downregulating ATM, DNA-PKcs, Ku70/80, and RAD51. Additionally, differential expression of miR-27a, miR-221, and miR-224 in treatment-sensitive versus treatment-resistant patients indicated their predictive biomarker potential for treatment response of cervical cancer patients. Conclusively, this study has identified 18 promising miRNAs for the development of sensitizers for thermoradiotherapy and may provide potential biomarkers for predicting treatment response in locally advanced cancers.

10 Apr 2025·Nucleic Acids Research

The linker region of a development-specific DNA polymerase X ensures efficient repair of programmed DNA double-strand breaks in Paramecium tetraurelia

Article

Author: Verron, Baptiste ; Bischerour, Julien ; Bétermier, Mireille ; Arnaiz, Olivier ; Zangarelli, Coralie ; Mathy, Nathalie

AbstractDuring the sexual cycle, programmed genome rearrangement in Paramecium tetraurelia involves the non-homologous end joining (NHEJ) DNA repair pathway to eliminate specific germinal internal eliminated sequences (IESs) from the newly developing somatic nucleus. Besides the core NHEJ factors Ku70/80 and Xrcc4/Lig4, additional enzymes are required to process the 4-base 5′-protruding ends generated following DNA cleavage at IES boundaries, prior to their ligation. Here, we report that PolXa,b,c,d, four P. tetraurelia distant orthologs of the human Polλ DNA polymerase, are involved in the repair of IES excision junctions. During rearrangements, PolX-depleted cells accumulate genome-wide errors, such as unrepaired double-strand breaks, one-nucleotide deletions, and IES retention. Although all PolX paralogs can process DNA ends, two of them (PolXa&b) are induced during rearrangements and have evolved a specific linker sequence downstream of their BRCT domain, which provides them with tight nuclear anchoring properties. We show that PolXa accumulates in nuclear foci together with other NHEJ actors and the Dicer-like enzyme Dcl5, which is involved in the biogenesis of IES-specific small RNAs. We propose that these ‘DNA repair foci’ correspond to the sites where IES concatemers, a by-product of IES excision, are ligated together to produce the precursors of these small RNAs.

20 Mar 2025·Nucleic Acids Research

Homeodomain protein PRRX1 anchors the Ku heterodimers at DNA double-strand breaks to promote nonhomologous end-joining

Article

Author: Gan, Jia ; Chen, Qiang ; Wang, Wen ; Zhou, Yan ; Zhang, Haojian ; Shen, Fuyuan ; Wang, Yan ; Wang, Fangyu ; Li, Jiali ; Liu, Ying ; Zhao, Chen ; Li, Yamu ; Chen, Xuefeng

AbstractThe DNA-dependent protein kinase (DNA–PK) complex plays a critical role in nonhomologous end-joining (NHEJ), a template-independent pathway for repairing DNA double-strand breaks (DSBs). The association of Ku70/80 with DSB ends facilitates the assembly of the DNA–PK holoenzyme. However, key mechanisms underlying the attachment and stabilization of DNA–PK at broken DNA ends remain unclear. Here, we identify PRRX1, a homeodomain-containing protein, as a mediator of chromatin localization and subsequent activation of DNA–PK. PRRX1 oligomerizes to simultaneously bind to double-strand DNA and the SAP (SAF-A/B, Acinus, and PIAS) domain of Ku70, thereby enhancing Ku anchoring at DSBs and stabilizing DNA–PK for efficient NHEJ repair. Reduced expression or pathogenic mutations of PRRX1 are associated with genomic instability and impaired NHEJ repair. Furthermore, a peptide that disrupts PRRX1 oligomerization compromises NHEJ efficiency and reduces cell survival following irradiation. These findings provide new insights into the activation of the NHEJ machinery and offer potential strategies for optimizing cancer therapies.

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Ku70/80

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