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DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers (2015)
Journal Article
Abdel-Fatah, T. M., Arora, A., Moseley, P. M., Perry, C., Rakha, E. A., Green, A. R., …Madhusudan, S. (2015). DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers. Oncotarget, 6(26), 21964-21978. https://doi.org/10.18632/oncotarget.4157

Stratification of oestrogen receptor (ER) negative and triple negative breast cancers (TNBCs) is urgently needed. In the current study, a cohort of 880 ER- (including 635 TNBCs) was immuno-profiled for a panel of DNA repair proteins including: Pol β,... Read More about DNA repair prognostic index modelling reveals an essential role for base excision repair in influencing clinical outcomes in ER negative and triple negative breast cancers.

Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents (2015)
Journal Article
Ong, C. C., Gierke, S., Pitt, C., Sagolla, M., Cheng, C. K., Zhou, W., …Hoeflich, K. P. (2015). Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Research, 17(1), Article 59. https://doi.org/10.1186/s13058-015-0564-5

Introduction Breast cancer, the most common cause of cancer-related deaths worldwide among women, is a molecularly and clinically heterogeneous disease. Extensive genetic and epigenetic profiling of breast tumors has recently revealed novel puta... Read More about Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents.

FKBPL: a marker of good prognosis in breast cancer (2015)
Journal Article
Nelson, L., McKeen, H. D., Ellis, I., Rakha, E., Marshall, A., Mulrane, L., …Robson, T. (2015). FKBPL: a marker of good prognosis in breast cancer. Oncotarget, 6(14), 12209-12223. https://doi.org/10.18632/oncotarget.3528

FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL’s prognostic ability in primary breast... Read More about FKBPL: a marker of good prognosis in breast cancer.

Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer (2015)
Journal Article
Abduljabbar, R., Negm, O. H., Lai, C., Jerjees, D. A., Al-Kaabi, M., Hamed, M. R., …Ellis, I. O. (2015). Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer. Breast Cancer Research and Treatment, 150(2), 335-346. https://doi.org/10.1007/s10549-015-3335-1

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels... Read More about Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

AKT and 14-3-3 regulate Notch4 nuclear localization (2015)
Journal Article
Ramakrishnan, G., Davaakhuu, G., Chung, W. C., Zhu, H., Rana, A., Filipovic, A., …Tzivion, G. (2015). AKT and 14-3-3 regulate Notch4 nuclear localization. Scientific Reports, 5(1), Article 8782. https://doi.org/10.1038/srep08782

Members of the Notch family of transmembrane receptors, Notch1-4 in mammals, are involved in the regulation of cell fate decisions and cell proliferation in various organisms. The Notch4 isoform, which is specific to mammals, was originally identifie... Read More about AKT and 14-3-3 regulate Notch4 nuclear localization.

The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways (2015)
Journal Article
Jerjees, D. A., Negm, O. H., Alabdullah, M. L., Mirza, S., Alkaabi, M., Hameed, M. R., …Rakha, E. A. (2015). The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways. Breast Cancer Research and Treatment, 150(1), 91-103. https://doi.org/10.1007/s10549-015-3308-4

The mammalian target of rapamycin complex 1 (mTORC1) is a downstream of the PI3K/Akt pathway which affects cancer development. mTORC1 has many downstream signalling effectors that can enhance different cellular responses. This study aims to investiga... Read More about The mammalian target of rapamycin complex 1 (mTORC1) in breast cancer: the impact of oestrogen receptor and HER2 pathways.

DNA damage response markers are differentially expressed in BRCA-mutated breast cancers (2015)
Journal Article
Aleskandarany, M., Caracappa, D., Nolan, C. C., Macmillan, R. D., Ellis, I. O., Rakha, E. A., & Green, A. R. (2015). DNA damage response markers are differentially expressed in BRCA-mutated breast cancers. Breast Cancer Research and Treatment, 150(1), 81-90. https://doi.org/10.1007/s10549-015-3306-6

Cells have stringent DNA repair pathways that are specific for each different set of DNA lesions which is accomplished through the integration of complex array of proteins. However, BRCA-mutated breast cancer (BC) has defective DNA repair mechanisms.... Read More about DNA damage response markers are differentially expressed in BRCA-mutated breast cancers.

Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response (2015)
Journal Article
Al-kaabi, M., Alshareeda, A., Jerjees, D., Muftah, A., Green, A., Alsubhi, N., …Rakha, E. (2015). Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response. British Journal of Cancer, 112(5), 901-911. https://doi.org/10.1038/bjc.2014.576

Background: Checkpoint kinase1 (CHK1), which is a key component of DNA-damage-activated checkpoint signalling response, may have a role in breast cancer (BC) pathogenesis and influence response to chemotherapy. This study investigated the clinicop... Read More about Checkpoint kinase1 (CHK1) is an important biomarker in breast cancer having a role in chemotherapy response.

Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer (2015)
Journal Article
Arora, A., Abdel-Fatah, T., Agarwal, D., Doherty, R., Moseley, P. M., Aleskandarany, M. A., …Madhusudan, S. (2015). Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer. Molecular Cancer Therapeutics, 14(4), https://doi.org/10.1158/1535-7163.MCT-14-0939

Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition... Read More about Transcriptomic and protein expression analysis reveals clinicopathological significance of bloom syndrome helicase (BLM) in breast cancer.

Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer (2014)
Journal Article
Davis, J., Martin, S. G., Patel, P. M., Green, A. R., Rakha, E. A., Ellis, I. O., & Storr, S. J. (2014). Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer. BMC Cancer, 14(1), https://doi.org/10.1186/1471-2407-14-995

Background The calpains are intracellular cysteine proteases that function in a variety of important cellular functions, including signalling, motility, apoptosis and survival. In breast cancer high calpain-1 and calpain-2 expression has been asso... Read More about Low calpain-9 is associated with adverse disease-specific survival following endocrine therapy in breast cancer.

Biological and clinical significance of PARP1 protein expression in breast cancer (2014)
Journal Article
Green, A. R., Caracappa, D., Benhasouna, A. A., Alshareeda, A., Nolan, C. C., Macmillan, R. D., …Rakha, E. A. (2015). Biological and clinical significance of PARP1 protein expression in breast cancer. Breast Cancer Research and Treatment, 149(2), 353-362. https://doi.org/10.1007/s10549-014-3230-1

Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinic... Read More about Biological and clinical significance of PARP1 protein expression in breast cancer.

Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer (2014)
Journal Article
Wishart, G. C., Rakha, E., Green, A., Ellis, I., Ali, H. R., Provenzano, E., …Pharoah, P. D. (2014). Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer. BMC Cancer, 14(1), Article 908. https://doi.org/10.1186/1471-2407-14-908

Background PREDICT (http://www.predict.nhs.uk) is a prognostication and treatment benefit tool for early breast cancer (EBC). The aim of this study was to incorporate the prognostic effect of KI67 status in a new version (v3), and compare performa... Read More about Inclusion of KI67 significantly improves performance of the PREDICT prognostication and prediction model for early breast cancer.

Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker (2014)
Journal Article
Mohammed, R. A., Menon, S., Martin, S. G., Green, A. R., Paish, E. C., & Ellis, I. O. (2014). Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker. Modern Pathology, 27(12), 1568-1577. doi:10.1038/modpathol.2014.60

Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts (2014)
Journal Article
Abdel-Fatah, T. M., Arora, A., Alsubhi, N., Agarwal, D., Moseley, P. M., Perry, C., …Madhusudan, S. (2014). Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts. Neoplasia, 16(11), 982-991. https://doi.org/10.1016/j.neo.2014.09.009

ATM-Chk2 network is critical for genomic stability, and its deregulation may influence breast cancer pathogenesis. We investigated ATM and Chk2 protein levels in two cohorts [cohort 1 (n = 1650) and cohort 2 (n = 252)]. ATM and Chk2 mRNA expression w... Read More about Clinicopathological significance of ATM-Chk2 expression in sporadic breast cancers: a comprehensive analysis in large cohorts.

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer (2014)
Journal Article
Abdel-Fatah, T. M., Middleton, F. K., Arora, A., Agarwal, D., Chen, T., Moseley, P. M., …Madhusudan, S. (2015). Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer. Molecular Oncology, 9(3), 569-585. https://doi.org/10.1016/j.molonc.2014.10.013

ATR?CHEK1 signalling is critical for genomic stability. ATR?CHEK1 signalling may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. We investigated ATR, CHEK1 and phosphorylated CHEK1 Ser345 protein (pCHEK1)... Read More about Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer.

Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy (2014)
Journal Article
Zhang, Y., Storr, S. J., Johnson, K., Green, A. R., Rakha, E. A., Ellis, I. O., …Martin, S. G. (2014). Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy. Oncotarget, 5(24), https://doi.org/10.18632/oncotarget.2683

Metformin is under evaluation as a potential anticancer agent. Expression of total and phospho(Thr172)-adenosine monophosphate-activated kinase-α (AMPKα and pAMPKα(Thr172) respectively), a main metformin target, was examined in radiotherapy treated b... Read More about Involvement of metformin and AMPK in the radioresponse and prognosis of luminal versus basal-like breast cancer treated with radiotherapy.

Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells (2014)
Journal Article
Filipović, A., Lombardo, Y., Fronato, M., Abrahams, J., Aboagye, E., Nguyen, Q., …Coombes, R. C. (2014). Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells. Breast Cancer Research and Treatment, 148(2), 455-462. https://doi.org/10.1007/s10549-014-3119-z

The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancie... Read More about Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells.

Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers? (2014)
Journal Article
Abdel-Fatah, T. M., Perry, C., Arora, A., Thompson, N., Doherty, R., Moseley, P. M., …Madhusudan, S. (2014). Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers?. Antioxidants and Redox Signaling, 21(16), 2262-2268. https://doi.org/10.1089/ars.2014.6077

Estrogen and estrogen metabolite-induced reactive oxygen species generation can promote oxidative DNA base damage. If unrepaired, base damaging lesions could accelerate mutagenesis, leading to a “mutator phenotype” characterized by aggressive behavio... Read More about Is there a role for base excision repair in estrogen/estrogen receptor-driven breast cancers?.

The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis (2014)
Journal Article
Ullenhag, G. J., Al-Attar, A., Mukherjee, A., Green, A. R., Ellis, I. O., & Durrant, L. G. (2015). The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis. Journal of Cancer Research and Clinical Oncology, 141(3), 505-514. doi:10.1007/s00432-014-1822-0

Background Breast cancer is the most common cancer in women. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway transmits apoptotic signals. Novel anticancer agents that activate this system are in clinical development, in... Read More about The TRAIL system is over-expressed in breast cancer and FLIP a marker of good prognosis.