Results 121 to 130 of about 1,770,471 (326)

Metabolic synthetic lethality in cancer therapy

Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2017
Our understanding of cancer has recently seen a major paradigm shift resulting in it being viewed as a metabolic disorder, and altered cellular metabolism being recognised as a hallmark of cancer. This concept was spurred by the findings that the oncogenic mutations driving tumorigenesis induce a reprogramming of cancer cell metabolism that is required
Zecchini, Vincent, Frezza, Christian
openaire   +3 more sources

KDM7A and KDM1A inhibition suppresses tumour promoting pathways in prostate cancer

Molecular Oncology, EarlyView.
Treatment resistance is a major challenge for patients with advanced prostate cancer. This study examined an alternative approach to target the major prostate cancer‐promoting pathway by targeting epigenetic factors, whose levels are higher in tumours.
Jennie N Jeyapalan, Veronika M Metzler, Simone de Brot, Corinne L Woodcock, Anna E Harris, Jennifer Lothion‐Roy, Emeli M Nilsson, Atara Ntekim, Michael S Toss, Jenny L Persson, Francesca Khani, Brian D Robinson, Lorraine J Gudas, Emad Rakha, David M Heery, Catrin S Rutland, Nigel P Mongan   +16 more
wiley   +1 more source

The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings

Molecular Oncology, 2011
Poly (ADP‐ribose) polymerase (PARP) inhibitors effectively kill tumours defective in the BRCA1 or BRCA2 genes through the concept of synthetic lethality. It is suggested that PARP inhibitors cause an increase in DNA single‐strand breaks (SSBs), which are
Thomas Helleday
doaj   +1 more source

Cell‐cycle‐specific lesion evolution rather than inhibition of double‐strand‐break repair underpins cisplatin radiosensitization

Molecular Oncology, EarlyView.
We analyze cisplatin–DNA adducts (CDAs) and double‐strand breaks (DSBs) in a cell‐cycle‐dependent manner. We find that CDAs form similarly across all cell cycle phases. DSBs arise only in S‐phase. CDAs might not directly impair DSB repair, but S‐phase DSB lesions evolve in the presence of CDAs and disrupt repair in G2, also causing radiosensitization ...
Ye Qiu, Xixi Lin, Emil Mladenov, Veronika Mladenova, Jürgen Thomale, Ali Sak, Yao Wang, Yunxuan Deng, Eleni Gkika, Martin Stuschke, George Iliakis   +10 more
wiley   +1 more source

Epigenetic based synthetic lethal strategies in human cancers

Biomarker Research, 2020
Over the past decades, it is recognized that loss of DNA damage repair (DDR) pathways is an early and frequent event in tumorigenesis, occurring in 40-50% of many cancer types.
Aiai Gao, Mingzhou Guo
doaj   +1 more source

Identification of a Small Molecule Inhibitor of RAD52 by Structure-Based Selection. [PDF]

PLoS ONE, 2016
It has been reported that inhibition of RAD52 either by specific shRNA or a small peptide aptamer induced synthetic lethality in tumor cell lines carrying BRCA1 and BRCA2 inactivating mutations. Molecular docking was used to screen two chemical libraries:
Katherine Sullivan, Kimberly Cramer-Morales, Daniel L McElroy, David A Ostrov, Kimberly Haas, Wayne Childers, Robert Hromas, Tomasz Skorski   +7 more
doaj   +1 more source

dUTPase is essential in zebrafish development and possesses several single‐nucleotide variants with pronounced structural and functional consequences

FEBS Open Bio, EarlyView.
dUTPases are involved in balancing the appropriate nucleotide pools. We showed that dUTPase is essential for normal development in zebrafish. The different zebrafish genomes contain several single‐nucleotide variations (SNPs) of the dut gene. One of the dUTPase variants displayed drastically lower protein stability and catalytic efficiency as compared ...
Viktória Perey‐Simon, Angéla Békesi, Latifa Kazzazy, Jázmin Mihály, Máté Varga, Beáta G. Vértessy, Kinga Nyíri   +6 more
wiley   +1 more source

TNG908 is a brain-penetrant, MTA-cooperative PRMT5 inhibitor developed for the treatment of MTAP-deleted cancers

Translational Oncology
: TNG908 is a clinical stage PRMT5 inhibitor with an MTA-cooperative binding mechanism designed to leverage the synthetic lethal interaction between PRMT5 inhibition and MTAP deletion.
Kimberly J. Briggs, Kevin M. Cottrell, Matthew R. Tonini, Alice Tsai, Minjie Zhang, Douglas A. Whittington, Wenhai Zhang, Steven A. Lombardo, Satoshi Yoda, Erik W. Wilker, Samuel R. Meier, Yi Yu, Teng Teng, Alan Huang, John P. Maxwell   +14 more
doaj   +1 more source

Defective cell cycle checkpoints as targets for anti-cancer therapies

Frontiers in Pharmacology, 2012
Conventional chemotherapeutics target the proliferating fraction of cells, which will include the tumour cells, but are also toxic to actively proliferating normal tissues.
Brian eGabrielli, Kelly eBrooks, Sandra ePavey   +2 more
doaj   +1 more source

Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens

Nature Communications, 2022
Synthetic lethality can be used to identify potential drug targets in cancer based on simultaneous inactivation of two genes through genetic aberrations and gene silencing.
Sumana Srivatsa, Hesam Montazeri, Gaia Bianco, Mairene Coto-Llerena, Mattia Marinucci, Charlotte K. Y. Ng, Salvatore Piscuoglio, Niko Beerenwinkel   +7 more
doaj   +1 more source