Results 1 to 10 of about 43,707 (255)

Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma

eLife, 2015
Human lung adenocarcinomas (LUAD) contain mutations in EGFR in ∼15% of cases and in KRAS in ∼30%, yet no individual adenocarcinoma appears to carry activating mutations in both genes, a finding we have confirmed by re-analysis of data from over 600 LUAD.
Arun M Unni, William W Lockwood, Kreshnik Zejnullahu, Shih-Queen Lee-Lin, Harold Varmus   +4 more
doaj   +1 more source

Increased H+ efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression

eLife, 2015
Intracellular pH (pHi) dynamics is increasingly recognized as an important regulator of a range of normal and pathological cell behaviors. Notably, increased pHi is now acknowledged as a conserved characteristic of cancers and in cell models is confirmed
Bree K Grillo-Hill, Changhoon Choi, Maite Jimenez-Vidal, Diane L Barber   +3 more
doaj   +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

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

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

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

Advances in synthetic lethality modalities for glioblastoma multiforme

Open Medicine
Glioblastoma multiforme (GBM) is characterized by a high mortality rate, high resistance to cytotoxic chemotherapy, and radiotherapy due to its highly aggressive nature.
Richard Seidu A.
doaj   +1 more source

An in-silico approach to predict and exploit synthetic lethality in cancer metabolism

Nature Communications, 2017
Exploiting synthetic lethality is a promising approach for cancer therapy. Here, the authors present an approach to identifying such interactions by finding genetic minimal cut sets (gMCSs) that block cancer proliferation, and apply it to study the ...
Iñigo Apaolaza, Edurne San José-Eneriz, Luis Tobalina, Estíbaliz Miranda, Leire Garate, Xabier Agirre, Felipe Prósper, Francisco J. Planes   +7 more
doaj   +1 more source

Therapeutic Role of Synthetic Lethality in ARID1A-Deficient Malignancies [PDF]

Journal of Immunotherapy and Precision Oncology
AT-rich interaction domain 1A (ARID1A), a mammalian switch/sucrose nonfermenting complex subunit, modulates several cellular processes by regulating chromatin accessibility.
Kyaw Z. Hein, Bettzy Stephen, Siqing Fu
doaj   +1 more source