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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 ...
Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin.
(NATURE PUBLISHING GROUP, 2020-01-21)
BACKGROUND: Epidemiological studies suggest that metformin may reduce the incidence of cancer in patients with diabetes and multiple late phase clinical trials assessing the potential of repurposing this drug are underway. ...
Cancer-Associated Fibroblasts Suppress CD8+ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade.
(AMER ASSOC CANCER RESEARCH, 2022-08-16)
UNLABELLED: Immune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover ...
Age-associated microenvironmental changes highlight the role of PDGF-C in ER+ breast cancer metastatic relapse.
(NATURE PORTFOLIO, 2023-04-01)
Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse for decades after primary tumor resection and treatment, a consequence of dormant disseminated tumor cells (DTCs) reawakening ...
Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis.
(NATURE PORTFOLIO, 2021-06-10)
Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is ...