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CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours.
(PUBLIC LIBRARY SCIENCE, 2016-02-16)
Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer.
(NATURE PORTFOLIO, 2020-09-17)
Genomic instability is a hallmark of cancer, and has a central role in the initiation and development of breast cancer1,2. The success of poly-ADP ribose polymerase inhibitors in the treatment of breast cancers that are ...
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 ...
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 ...
ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A.
(NATURE PUBLISHING GROUP, 2016-12-13)
Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
Modeling Therapy Resistance in BRCA1/2-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ...
Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer.
(BMJ PUBLISHING GROUP, 2018-10-01)
OBJECTIVE: Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN: To identify new biomarker-defined therapeutic approaches ...
Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib.
(AMER ASSOC CANCER RESEARCH, 2016-07-01)
New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based ...