Results 61 to 70 of about 52,625 (269)

Loss of IGF‐1R impairs DNA‐PKcs recruitment to chromatin leading to defective end‐joining

Molecular Oncology, EarlyView.
IGF‐1R promotes radioresistance by facilitating DNA‐PKcs recruitment to chromatin, enabling non‐homologous end‐joining (NHEJ) repair of double‐strand breaks. Inhibition or loss of IGF‐1R disrupts this recruitment to damage sites, driving compensatory reliance on microhomology‐mediated end‐joining (MMEJ) repair.
Matthew O. Ellis, Jack V. Mills, Wojciech Niedzwiedz, Valentine M. Macaulay   +3 more
wiley   +1 more source

PARP Inhibitors in Ovarian Cancer: The Route to “Ithaca”

Diagnostics, 2019
Poly (ADP-ribose) polymerase (PARP) inhibitors are a novel class of therapeutic agents that target tumors with deficiencies in the homologous recombination DNA repair pathway.
Stergios Boussios, Afroditi Karathanasi, Deirdre Cooke, Cherie Neille, Agne Sadauskaite, Michele Moschetta, Nikolaos Zakynthinakis-Kyriakou, Nicholas Pavlidis   +7 more
doaj   +1 more source

Homologous Recombination Deficiency Score Determined by Genomic Instability in a Romanian Cohort

Diagnostics, 2023
The Homologous Recombination Deficiency (HRD) Score, determined by evaluating genomic instability through the assessment of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST), serves as a crucial ...
Viorica-Elena Rădoi, Mihaela Țurcan, Ovidiu Virgil Maioru, Andra Dan, Laurentiu Camil Bohîlțea, Elena Adriana Dumitrescu, Adelina Silvana Gheorghe, Dana Lucia Stănculeanu, Georgia Thodi, Yannis L. Loukas, Ileana-Delia Săbău   +10 more
doaj   +1 more source

Finding novel vulnerabilities of hypomorphic BRCA1 alleles

Molecular Oncology, EarlyView.
Synthetic lethality screens performed to identify novel vulnerabilities often model complete gene loss, thereby overlooking patient‐derived hypomorphic mutations. In this study, we have performed genome‐wide CRISPR screens on BRCA1 hypomorphic mutations, showing BRCA1I26A behaves like wild‐type, while BRCA1R1699Q mimics deficiency. Furthermore, we have
Anne Schreuder, Klaas de Lint, Hồ Mỹ Phúc Võ, Mariana M. Góis, Rosalie A. Kampen, Marta San Martin Alonso, Ilse Nootenboom, Veronica Garzero, Tiemen J. Wendel, Rob M. F. Wolthuis, Sylvie M. Noordermeer   +10 more
wiley   +1 more source

Indications and timing for genetic testing in ovarian cancer

Journal of Medical Science
Modern management of ovarian cancer (OC) relies on molecular diagnostics, with genetic testing playing a central role in therapeutic decisions. High-grade serous ovarian cancer (HGSOC) is frequently associated with mutations in the BRCA1 and BRCA2 genes,
Cezary Miedziarek, Maksymilian Markwitz, Michał Potograbski, Mikołaj Piotr Zaborowski   +3 more
doaj   +1 more source

Homologous recombination deficiency derived from whole-genome sequencing predicts platinum response in triple-negative breast cancers

Nature Communications, 2023
Homologous recombination deficiency is linked with platinum-based chemotherapy response in triple-negative breast cancer (TNBC) but methods to clinically identify these patients are lacking.
Petra ter Brugge, Sarah C. Moser, Ivan Bièche, Petra Kristel, Sabrina Ibadioune, Alexandre Eeckhoutte, Roebi de Bruijn, Eline van der Burg, Catrin Lutz, Stefano Annunziato, Julian de Ruiter, Julien Masliah Planchon, Sophie Vacher, Laura Courtois, Rania El-Botty, Ahmed Dahmani, Elodie Montaudon, Ludivine Morisset, Laura Sourd, Léa Huguet, Heloise Derrien, Fariba Nemati, Sophie Chateau-Joubert, Thibaut Larcher, Anne Salomon, Didier Decaudin, Fabien Reyal, Florence Coussy, Tatiana Popova, Jelle Wesseling, Marc-Henri Stern, Jos Jonkers, Elisabetta Marangoni   +32 more
doaj   +1 more source

Inhibition of cyclin‐dependent kinases 12/13 using CT7439 as a treatment for colorectal cancer with CDK12 upregulation

Molecular Oncology, EarlyView.
The proposed mechanism of action for the CDK12/13 inhibitor and cyclin K degrader, CT7439. CDK12/13 inhibition interrupts transcription elongation, leading to increased DNA damage that results in cell death. This agent is a potentially novel treatment option for patients with colorectal cancer. Created in BioRender. Cyclin‐dependent kinase (CDK) 12 and
Wylie K. Watlington, Divya L. Dayanidhi, Mohammad Zokaasadi, John B. Mantyh, Pelumi D. Olawuni, Gabrielle Rupprecht, Jeremy M. Force, Shannon McCall, Ashwani K. Bahl, David S. Hsu, Jason A. Somarelli   +10 more
wiley   +1 more source

Implementation of a stepwise process for somatic testing in patients with a new diagnosis of germline negative epithelial ovarian cancer

Gynecologic Oncology Reports
Objective: We sought to establish a process for increasing somatic tumor testing for patients with germline BRCA negative advanced stage epithelial ovarian cancer (EOC) and to gain insight into patients’ comprehension of their genetic testing. Methods: A
Casey L. Lawler, Sara M. Klennert, Kristin C. Cole, Karen S. Schaepe, Laura J. Ongie, Megan E. Grudem, Carolyn M. Klampe, Myra J. Wick, Vonda M. Wall, Sanjna Rajput, Clarissa L. Polen-De, Amanika Kumar   +11 more
doaj   +1 more source

Using whole-genome sequencing data to derive the homologous recombination deficiency scores

, 2020
The homologous recombination deficiency (HRD) score was developed using whole-genome copy number data derived from arrays as a way to infer deficiency in the homologous recombination DNA damage repair pathway (in particular BRCA1 or BRCA2 deficiency) in ...
McCart Reed, Amy E., Leonard, Conrad, Simpson, Peter T., de Luca, Xavier M., Waddell, Nicola, Holmes, Oliver, Lakhani, Sunil R., Xu, Qinying, Newell, Felicity, Kazakoff, Stephen H., Pearson, John V., Hartel, Gunter, Nones, Katia, Wood, Scott   +13 more
core   +1 more source

Proteasomal degradation of intracellularly expressed Amblyomin‐X limits suicide gene therapy potential in melanoma cells

FEBS Open Bio, EarlyView.
This study explores the feasibility of expressing the antitumoral protein Amblyomin‐X through a suicide gene therapy approach and investigates its intracellular fate after gene delivery. Although the gene is efficiently expressed, melanoma cells rapidly degrade the Amblyomin‐X protein via proteasome activity.
Victor Dal Posolo Cinel, Carlos DeOcesano Pereira, Aline Ramos Maia Lobba, Melissa Regina Fessel, Ana Marisa Chudzinski‐Tavassi   +4 more
wiley   +1 more source