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Driver Oncogenes but Not as We Know Them: Targetable Fusion Genes in Breast Cancer.
(2018-03)
<b/> Two reports in this issue of Cancer Discovery outline how the genomic composition of tumors, including the presence of intragenic gene fusions, could inform the selection of treatment approaches in aggressive forms ...
Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels.
(HUMANA PRESS INC, 2018-01-01)
Loss-of-function screening using RNA interference or CRISPR approaches can be used to identify genes that specific tumor cell lines depend upon for survival. By integrating the results from screens in multiple cell lines ...
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-04-01)
The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2018-01-01)
Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. ...
Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.
(CELL PRESS, 2018-01-30)
Approximately 30% of triple-negative breast cancers (TNBCs) exhibit functional loss of the RB tumor suppressor, suggesting a target for precision intervention. Here, we use drug screens to identify agents specifically ...
DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.
(AMER SOC CLINICAL INVESTIGATION INC, 2018-04-02)
Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer ...
Synthetic Lethality and Cancer - Penetrance as the Major Barrier.
(CELL PRESS, 2018-10-01)
Synthetic lethality has long been proposed as an approach for targeting genetic defects in tumours. Despite a decade of screening efforts, relatively few robust synthetic lethal targets have been identified. Improved genetic ...
Synthetic lethal therapies for cancer: what's next after PARP inhibitors?
(NATURE PUBLISHING GROUP, 2018-06-28)
The genetic concept of synthetic lethality has now been validated clinically through the demonstrated efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of cancers in individuals with germline ...
Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets.
(NATURE PUBLISHING GROUP, 2018-05-22)
Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...
Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers.
(WILEY, 2018-07-20)
ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ...