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CancerGD: A Resource for Identifying and Interpreting Genetic Dependencies in Cancer.
(CELL PRESS, 2017-07-26)
Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ...
Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes.
(AMER ASSOC CANCER RESEARCH, 2017-08-15)
Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical ...
Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells.
(AMER ASSOC CANCER RESEARCH, 2017-11-01)
Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and ...
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 ...
An In Vivo Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Chemotherapy remains the mainstay of treatment for advanced breast cancer; however, resistance is an inevitable event for the majority of patients with metastatic disease. Moreover, there is little information available ...
Src Is a Potential Therapeutic Target in Endocrine-Resistant Breast Cancer Exhibiting Low Estrogen Receptor-Mediated Transactivation.
(PUBLIC LIBRARY SCIENCE, 2016-06-16)
Despite the effectiveness of endocrine therapies in estrogen receptor positive (ER+) breast cancer, approximately 40% of patients relapse. Previously, we identified the Focal-adhesion kinase canonical pathway as a major ...
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.
(NATURE PORTFOLIO, 2023-08-01)
SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells ...
MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells.
(CELL PRESS, 2023-05-30)
The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity ...
Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities.
(SPRINGERNATURE, 2020-06-18)
Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than ...