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Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
(NATURE RESEARCH, 2021-06-17)
To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ...
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 ...
A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics.
(AMER ASSOC CANCER RESEARCH, 2019-01-01)
The molecular complexity of triple-negative breast cancers (TNBCs) provides a challenge for patient management. We set out to characterize this heterogeneous disease by combining transcriptomics and genomics data, with the ...
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 ...