Browsing Breast Cancer Research by author "Tutt, Andrew"
Now showing items 1-20 of 32
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3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer.
Peck, B; Bland, P; Mavrommati, I; Muirhead, G; Cottom, H; et al. (AMER ASSOC CANCER RESEARCH, 2021-02-15)Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies ... -
A decade of clinical development of PARP inhibitors in perspective.
Mateo, J; Lord, CJ; Serra, V; Tutt, A; Balmaña, J; et al. (ELSEVIER, 2019-09-01)Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ... -
A Four-gene Decision Tree Signature Classification of Triple-negative Breast Cancer: Implications for Targeted Therapeutics.
Quist, J; Mirza, H; Cheang, MCU; Telli, ML; O'Shaughnessy, JA; et al. (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 ... -
Assessing CSF ctDNA to Improve Diagnostic Accuracy and Therapeutic Monitoring in Breast Cancer Leptomeningeal Metastasis.
Fitzpatrick, A; Iravani, M; Mills, A; Childs, L; Alaguthurai, T; et al. (AMER ASSOC CANCER RESEARCH, 2022-03-15)PURPOSE: Cerebrospinal fluid (CSF) cytology is the gold standard diagnostic test for breast cancer leptomeningeal metastasis (BCLM), but has impaired sensitivity, often necessitating repeated lumbar puncture to confirm or ... -
Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.
Baxter, JS; Brough, R; Krastev, DB; Song, F; Sridhar, S; et al. (WILEY, 2023-10-22)The F-box and WD repeat domain containing 7 (FBXW7) tumour suppressor gene encodes a substrate-recognition subunit of Skp, cullin, F-box (SCF)-containing complexes. The tumour-suppressive role of FBXW7 is ascribed to its ... -
Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.
Tutt, A; Tovey, H; Cheang, MCU; Kernaghan, S; Kilburn, L; et al. (NATURE PUBLISHING GROUP, 2018-04-30)Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs ... -
Clinical BRCA1/2 Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance.
Pettitt, SJ; Frankum, JR; Punta, M; Lise, S; Alexander, J; et al. (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.
Fitzpatrick, A; Tutt, A (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 ... -
Driver Oncogenes but Not as We Know Them: Targetable Fusion Genes in Breast Cancer.
Natrajan, R; Tutt, ANJ; Lord, CJ (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 ... -
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer.
Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; et al. (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 ... -
Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer.
Naidoo, K; Wai, PT; Maguire, SL; Daley, F; Haider, S; et al. (AMER ASSOC CANCER RESEARCH, 2018-01-01)Disruption of Cyclin-Dependent Kinase 12 (CDK12) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, CDK12 has also been proposed as an oncogene in breast cancer. ... -
Gene expression modules in primary breast cancers as risk factors for organotropic patterns of first metastatic spread: a case control study.
Lawler, K; Papouli, E; Naceur-Lombardelli, C; Mera, A; Ougham, K; et al. (BMC, 2017-10-13)BACKGROUND: Metastases from primary breast cancers can involve single or multiple organs at metastatic disease diagnosis. Molecular risk factors for particular patterns of metastastic spread in a clinical population are ... -
Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype.
Fitzpatrick, A; Iravani, M; Mills, A; Vicente, D; Alaguthurai, T; et al. (Springer Science and Business Media LLC, 2023-11-16)Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty ... -
Histological scoring of immune and stromal features in breast and axillary lymph nodes is prognostic for distant metastasis in lymph node-positive breast cancers.
Grigoriadis, A; Gazinska, P; Pai, T; Irhsad, S; Wu, Y; et al. (WILEY, 2018-01-08)The prognostic importance of lymph node (LN) status and tumour-infiltrating lymphocytes (TILs), is well established, particularly TILs in triple negative breast cancers (TNBCs). So far, few studies have interrogated changes ... -
Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer.
Chopra, N; Tovey, H; Pearson, A; Cutts, R; Toms, C; et al. (NATURE PORTFOLIO, 2020-05-29)Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO ... -
A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant.
Pettitt, SJ; Shao, N; Zatreanu, D; Frankum, J; Bajrami, I; et al. (SPRINGERNATURE, 2023-09-01)Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ... -
Integrated genomics and functional validation identifies malignant cell specific dependencies in triple negative breast cancer.
Patel, N; Weekes, D; Drosopoulos, K; Gazinska, P; Noel, E; et al. (NATURE PUBLISHING GROUP, 2018-03-13)Triple negative breast cancers (TNBCs) lack recurrent targetable driver mutations but demonstrate frequent copy number aberrations (CNAs). Here, we describe an integrative genomic and RNAi-based approach that identifies ... -
Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
Harvey-Jones, E; Raghunandan, M; Robbez-Masson, L; Magraner-Pardo, L; Alaguthurai, T; et al. (Elsevier BV, 2024-01-19)BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, ... -
Loss of E-cadherin leads to Id2-dependent inhibition of cell cycle progression in metastatic lobular breast cancer.
Rätze, MAK; Koorman, T; Sijnesael, T; Bassey-Archibong, B; van de Ven, R; et al. (SPRINGERNATURE, 2022-05-20)Invasive lobular breast carcinoma (ILC) is characterized by proliferative indolence and long-term latency relapses. This study aimed to identify how disseminating ILC cells control the balance between quiescence and cell ... -
MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells.
Zelceski, A; Francica, P; Lingg, L; Mutlu, M; Stok, C; et al. (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 ...