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Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells.
(NATURE PUBLISHING GROUP, 2018-08-01)
BRCA1 deficiencies cause breast, ovarian, prostate and other cancers, and render tumours hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. To understand the resistance mechanisms, we conducted whole-genome ...
Chlorambucil targets BRCA1/2-deficient tumours and counteracts PARP inhibitor resistance.
(WILEY, 2019-07-01)
Due to compromised homologous recombination (HR) repair, BRCA1- and BRCA2-mutated tumours accumulate DNA damage and genomic rearrangements conducive of tumour progression. To identify drugs that target specifically ...
ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response.
(NATURE PORTFOLIO, 2020-02-01)
Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the factors most critically ...
The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.
(CELL PRESS, 2019-10-22)
Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the ...
Validation of the OncoMasTR Risk Score in Estrogen Receptor-Positive/HER2-Negative Patients: A TransATAC study.
(AMER ASSOC CANCER RESEARCH, 2020-02-01)
PURPOSE: To test the validity of OncoMasTR Molecular Score (OMm), OMclin1, and OncoMasTR Risk Score (OMclin2) prognostic scores for prediction of distant recurrence (DR) in estrogen receptor (ER)-positive/HER2-negative ...
Topological Tumor Graphs: A Graph-Based Spatial Model to Infer Stromal Recruitment for Immunosuppression in Melanoma Histology.
(AMER ASSOC CANCER RESEARCH, 2020-03-01)
Despite the advent of immunotherapy, metastatic melanoma represents an aggressive tumor type with a poor survival outcome. The successful application of immunotherapy requires in-depth understanding of the biological basis ...
Inactivating NF1 Mutations Are Enriched in Advanced Breast Cancer and Contribute to Endocrine Therapy Resistance.
(AMER ASSOC CANCER RESEARCH, 2020-02-01)
PURPOSE: Advanced breast cancer (ABC) has not been subjected to the same degree of molecular scrutiny as early primary cancer. Breast cancer evolves with time and under the selective pressure of treatment, with the potential ...
ABC-transporter upregulation mediates resistance to the CDK7 inhibitors THZ1 and ICEC0942.
(NATURE PUBLISHING GROUP, 2020-01-01)
The CDK7 inhibitors (CDK7i) ICEC0942 and THZ1, are promising new cancer therapeutics. Resistance to targeted drugs frequently compromises cancer treatment. We sought to identify mechanisms by which cancer cells may become ...
IGF signalling in germ cells and testicular germ cell tumours: roles and therapeutic approaches.
(WILEY, 2019-07-01)
The insulin-like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their subsequent growth and progression to a metastatic phenotype. ...
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.
(CELL PRESS, 2019-06-26)
Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ...