Results 31 to 40 of about 1,770,471 (326)

Targeting the TCA cycle through cuproptosis confers synthetic lethality on ARID1A-deficient hepatocellular carcinoma

Cell Reports Medicine, 2023
Summary ARID1A is among the most commonly mutated tumor suppressor genes in hepatocellular carcinoma (HCC). In this study, we conduct a CRISPR-Cas9 synthetic lethality screen using ARID1A-deficient HCC cells to identify approaches to treat HCC patients ...
Tao Xing, Li Li, Yiran Chen, G. Ju, Guilan Li, Xiaoyu Zhu, Yubo Ren, Jing Zhao, Zhilei Cheng, Yan Li, Da Xu, Junyu Liang   +11 more
semanticscholar   +1 more source

Connectivity Homology Enables Inter-Species Network Models of Synthetic Lethality. [PDF]

PLoS Computational Biology, 2015
Synthetic lethality is a genetic interaction wherein two otherwise nonessential genes cause cellular inviability when knocked out simultaneously.
Alexandra Jacunski, Scott J Dixon, Nicholas P Tatonetti   +2 more
doaj   +1 more source

Paralog-based synthetic lethality: rationales and applications

Frontiers in Oncology, 2023
Tumor cells can result from gene mutations and over-expression. Synthetic lethality (SL) offers a desirable setting where cancer cells bearing one mutated gene of an SL gene pair can be specifically targeted by disrupting the function of the other genes,
Yucui Xin, Yingsheng Zhang
doaj   +1 more source

Nimbolide targets RNF114 to induce the trapping of PARP1 and synthetic lethality in BRCA-mutated cancer

Science Advances, 2023
Recent studies have pointed to PARP1 trapping as a key determinant of the anticancer effects of PARP1 inhibitors (PARPi). We identified RNF114, as a PARylation-dependent, E3 ubiquitin ligase involved in DNA damage response.
Peng Li, Yuanli Zhen, Chiho Kim, Zhengshuai Liu, Jianwei Hao, Heping Deng, Hejun Deng, Min Zhou, Xu-dong Wang, Tian Qin, Yonghao Yu   +10 more
semanticscholar   +1 more source

MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer

Cancer Discovery, 2023
Targeting the PRMT5/MTA complex selectively inhibits growth of MTAP-deleted preclinical cancer models and demonstrates preliminary clinical activity in MTAP-deleted cancers.
Lars D. Engstrom, Ruth Aranda, Laurie Waters, K. Moya, Vickie Bowcut, Laura Vegar, David Trinh, Allan Hebbert, Christopher R. Smith, Svitlana Kulyk, J. Lawson, Leo He, Laura D Hover, J. Fernandez-Banet, Jill Hallin, Darin Vanderpool, David M Briere, Alice Blaj, M. Marx, J. Rodón, M. Offin, K. Arbour, M. Johnson, D. Kwiatkowski, P. Janne, C. Haddox, K. Papadopoulos, Jason T Henry, Konstantinos Leventakos, J. Christensen, R. Shazer, Peter Olson   +31 more
semanticscholar   +1 more source

The potential and challenges of targeting MTAP-negative cancers beyond synthetic lethality

Frontiers in Oncology, 2023
Approximately 15% of cancers exhibit loss of the chromosomal locus 9p21.3 – the genomic location of the tumour suppressor gene CDKN2A and the methionine salvage gene methylthioadenosine phosphorylase (MTAP).
Chandler Bray, C. Balcells, I. McNeish, Hector C. Keun   +3 more
semanticscholar   +1 more source

The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment

Journal of Hematology & Oncology, 2022
Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division.
Shuangyi Li, Liang-Yan Wang, Yuanyuan Wang, Changyi Zhang, Z. Hong, Zhiqiang Han   +5 more
semanticscholar   +1 more source

Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency

Communications Biology, 2021
Bajrami, Walker et al. investigated the synthetic lethality between BRCA gene defects and inhibition of two sirtuin genes, SIRT1 or SIRT6, which was found to be associated with replication stress and increased PARylation.
Ilirjana Bajrami, Callum Walker, Dragomir B. Krastev, Daniel Weekes, Feifei Song, Andrew J. Wicks, John Alexander, Syed Haider, Rachel Brough, Stephen J. Pettitt, Andrew N. J. Tutt, Christopher J. Lord   +11 more
doaj   +1 more source

Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency

Molecules and Cells, 2021
SUMMARY Mutations in BRCA1 or BRCA2 (BRCA) is synthetic lethal with poly(ADP-ribose) polymerase inhibitors (PARPi). Lethality is thought to derive from DNA double-stranded breaks (DSBs) necessitating BRCA function in homologous recombination (HR) and/or ...
Ke Cong, Min Peng, A. N. Kousholt, W. T. C. Lee, S. Lee, Sumeet U. Nayak, J. Krais, P. VanderVere-Carozza, K. Pawelczak, J. Calvo, Nicholas J. Panzarino, J. Jonkers, N. Johnson, J. Turchi, E. Rothenberg, S. Cantor   +15 more
semanticscholar   +1 more source

The Population Genetics of Synthetic Lethals [PDF]

Genetics, 1998
Abstract Synthetic lethals are variants at different loci that have little or no effect on viability singly but cause lethality in combination. The importance of synthetic lethals and, more generally, of synthetic deleterious loci (SDL) has been controversial.
P C, Phillips, N A, Johnson
openaire   +2 more sources