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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 ...
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
(NATURE PUBLISHING GROUP, 2016-06-02)
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding ...
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 ...
PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.
(AMER SOC CLINICAL INVESTIGATION INC, 2019-03-01)
The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA ...
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance.
(AMER ASSOC CANCER RESEARCH, 2020-10-01)
Reversion mutations in BRCA1 or BRCA2 are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 reversions. This ...
Controversial issues in the neoadjuvant treatment of triple-negative breast cancer.
(SAGE PUBLICATIONS LTD, 2019-10-01)
Triple-negative breast cancer (TNBC), as a collective group of heterogenous tumours, displays the highest rate of distant recurrence and lowest survival from metastatic disease across breast cancer subtypes. However, a ...
Real-time ex vivo perfusion of human lymph nodes invaded by cancer (REPLICANT): a feasibility study.
(WILEY, 2020-03-01)
Understanding how breast cancer (BC) grows in axillary lymph nodes (ALNs), and refining how therapies might halt that process, is clinically important. However, modelling the complex ALN microenvironment is difficult, and ...
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 ...