Browsing Molecular Pathology by author "Tutt, Andrew"
Now showing items 1-17 of 17
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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 ... -
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 ... -
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 ... -
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 ... -
PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.
Chabanon, RM; Muirhead, G; Krastev, DB; Adam, J; Morel, D; et al. (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 ... -
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
Zatreanu, D; Robinson, HMR; Alkhatib, O; Boursier, M; Finch, H; et al. (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 ... -
Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment.
Stevenson, J; Barrow-McGee, R; Yu, L; Paul, A; Mansfield, D; et al. (NATURE PORTFOLIO, 2021-03-05)In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using ... -
Real-time ex vivo perfusion of human lymph nodes invaded by cancer (REPLICANT): a feasibility study.
Barrow-McGee, R; Procter, J; Owen, J; Woodman, N; Lombardelli, C; et al. (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 ... -
Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency.
Bajrami, I; Walker, C; Krastev, DB; Weekes, D; Song, F; et al. (NATURE PORTFOLIO, 2021-11-08)PARP enzymes utilise NAD+ as a co-substrate for their enzymatic activity. Inhibition of PARP1 is synthetic lethal with defects in either BRCA1 or BRCA2. In order to assess whether other genes implicated in NAD+ metabolism ... -
Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer.
Yeow, ZY; Lambrus, BG; Marlow, R; Zhan, KH; Durin, M-A; et al. (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 ... -
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.
Krastev, DB; Li, S; Sun, Y; Wicks, AJ; Hoslett, G; et al. (NATURE PORTFOLIO, 2022-01-01)Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using ...