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ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer (2024)
Journal Article
Patel, R., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (in press). ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer. Pathobiology, https://doi.org/10.1159/000539564

Purpose: ATF4, a stress-responsive transcription factor that upregulates adaptive genes, is a potential prognostic marker and modulator of glutamine metabolism in breast cancer. However, its exact role remains to be elucidated. Methods: ATF4 expre... Read More about ATF4 as a Prognostic Marker and Modulator of Glutamine Metabolism in Estrogen Receptor Positive Breast Cancer.

Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype (2024)
Journal Article
Makhlouf, S., Atallah, N. M., Polotto, S., Lee, A. H., Green, A. R., & Rakha, E. A. (2024). Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype. Cancers, 16(10), Article 1893. https://doi.org/10.3390/cancers16101893

Background: Invasive lobular carcinoma (ILC), the most common special type of breast cancer (BC), has unique clinical behaviour and is different from invasive ductal carcinoma of no special type (IDC-NST). However, ILC further comprises a diverse gro... Read More about Deciphering the Clinical Behaviour of Invasive Lobular Carcinoma of the Breast Defines an Aggressive Subtype.

Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study (2024)
Journal Article
Azam, A. S., Tsang, Y., Thirlwall, J., Kimani, P. K., Sah, S., Gopalakrishnan, K., …Snead, D. R. J. (2024). Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study. Histopathology, 84(5), 847-862. https://doi.org/10.1111/his.15129

Aims: To conduct a definitive multicentre comparison of digital pathology (DP) with light microscopy (LM) for reporting histopathology slides including breast and bowel cancer screening samples. Methods: A total of 2024 cases (608 breast, 607 GI, 6... Read More about Digital pathology for reporting histopathology samples, including cancer screening samples – definitive evidence from a multisite study.

The amino acid transporter SLC7A11 expression in breast cancer (2023)
Journal Article
Nath, P., Alfarsi, L. H., El-Ansari, R., Masisi, B. K., Erkan, B., Fakroun, A., …Green, A. R. (2024). The amino acid transporter SLC7A11 expression in breast cancer. Cancer Biology and Therapy, 25(1), Article 2291855. https://doi.org/10.1080/15384047.2023.2291855

Breast cancer (BC), characterized by its diverse molecular profiles and clinical outcomes, presents a significant challenge in the development of effective therapeutic strategies. Metabolic reprogramming, a defining characteristic of cancer, has emer... Read More about The amino acid transporter SLC7A11 expression in breast cancer.

Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways (2023)
Journal Article
Saidy, B., Vasan, R., Durant, R., Greener, M., Immanuel, A., Green, A. R., …Storr, S. J. (2023). Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways. Scientific Reports, 13(1), Article 21163. https://doi.org/10.1038/s41598-023-48198-y

DARPP-32 is a key regulator of protein-phosphatase-1 (PP-1) and protein kinase A (PKA), with its function dependent upon its phosphorylation state. We previously identified DKK1 and GRB7 as genes with linked expression using Artificial Neural Network... Read More about Unravelling transcriptomic complexity in breast cancer through modulation of DARPP-32 expression and signalling pathways.

The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion (2023)
Journal Article
Aljohani, A., Alsaeed, S., Toss, M., Raafat, S., GREEN, A., & Rakha, E. (2023). The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion. American Journal of Cancer Research, 13(11), 5334–5351

Lymphovascular invasion (LVI) is a common phenomenon in breast cancer (BC), and it is correlated to poor outcome. However, the biomarkers that influence the development of LVI remain to be defined. Through rigorous bioinformatics analyses, high mobil... Read More about The expression of high mobility group protein 3 (HMGB3) in breast cancer with emphasis on its role in lymphovascular invasion.

Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level (2023)
Journal Article
Atallah, N. M., Alsaleem, M., Toss, M. S., Mongan, N. P., & Rakha, E. (2023). Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level. British Journal of Cancer, https://doi.org/10.1038/s41416-023-02426-4

Background: Increasing data indicate that HER2-positive (HER2 +) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechani... Read More about Differential response of HER2-positive breast cancer to anti-HER2 therapy based on HER2 protein expression level.

Obesity-associated changes in molecular biology of primary breast cancer (2023)
Journal Article
Nguyen, H., Geukens, T., Maetens, M., Aparicio, S., Bassez, A., Borg, A., …Desmedt, C. (2023). Obesity-associated changes in molecular biology of primary breast cancer. Nature Communications, 14, Article 4418. https://doi.org/10.1038/s41467-023-39996-z

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs acc... Read More about Obesity-associated changes in molecular biology of primary breast cancer.

The clinical and biological significance of estrogen receptor-low positive breast cancer (2023)
Journal Article
Makhlouf, S., Althobi, M., Toss, M., Muftah, A. A., Mongan, N. P., Lee, A. H. S., …Rakha, E. A. (2023). The clinical and biological significance of estrogen receptor-low positive breast cancer. Modern Pathology, 36(10), Article 100284. https://doi.org/10.1016/j.modpat.2023.100284

Estrogen Receptor (ER) status in breast cancer (BC) is determined using immunohistochemistry (IHC) with nuclear expression in ≥1% of cells defined as ER-positive. BC with 1-9% expression (ER-low positive), is a clinically and biologically unique subg... Read More about The clinical and biological significance of estrogen receptor-low positive breast cancer.

Encapsulated papillary carcinoma of the breast: does it have a native basement membrane? (2023)
Journal Article
Ghannam, S. F., Rutland, C. S., Allegrucci, C., Mongan, N. P., & Rakha, E. (2023). Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?. Histopathology, 83(3), 376-393. https://doi.org/10.1111/his.14939

Background Encapsulated papillary carcinoma (EPC) is surrounded by a thick fibrous capsule-like structure, which is interpreted as a thickened basement membrane (BM). This study aimed to describe the geometric characteristics of the EPC capsule and... Read More about Encapsulated papillary carcinoma of the breast: does it have a native basement membrane?.

A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease (2023)
Journal Article
Storr, S. J., Hoskin, V., Aiyappa‐Maudsley, R., Ghaffari, A., Varma, S., Green, A., …Martin, S. G. (2023). A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease. Cancer Medicine, 12(9), 10908-10916. https://doi.org/10.1002/cam4.5802

Introduction: The cytoskeletal protein ezrin is upregulated in many cancer types and is strongly associated with poor patient outcome. While the clinical and prognostic value of ezrin has been previously evaluated in breast cancer, most studies to da... Read More about A retrospective analysis of ezrin protein and mRNA expression in breast cancer: Ezrin expression is associated with patient survival and survival of patients with receptor-positive disease.

RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer (2023)
Journal Article
Ciscar, M., Trinidad, E. M., Perez-Chacon, G., Alsaleem, M., Jimenez, M., Jimenez-Santos, M. J., …Gonzalez-Suarez, E. (2023). RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer. EMBO Molecular Medicine, 15(4), Article e16715. https://doi.org/10.15252/emmm.202216715

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein ex... Read More about RANK is a poor prognosis marker and a therapeutic target in ER-negative postmenopausal breast cancer.

Expression, assessment and significance of Ki67 expression in breast cancer: an update (2023)
Journal Article
Lashen, A. G., Toss, M. S., Ghannam, S. F., Makhlouf, S., Green, A., Mongan, N. P., & Rakha, E. (2023). Expression, assessment and significance of Ki67 expression in breast cancer: an update. Journal of Clinical Pathology, 76(6), Article 357-364. https://doi.org/10.1136/jcp-2022-208731

Ki67 expression is one of the most important and cost-effective surrogate markers to assess for tumour cell proliferation in breast cancer (BC). The Ki67 labelling index has prognostic and predictive value in patients with early-stage BC, particularl... Read More about Expression, assessment and significance of Ki67 expression in breast cancer: an update.

The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up (2023)
Journal Article
Lashen, A. G., Toss, M. S., Mongan, N. P., Green, A. R., & Rakha, E. A. (2023). The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up. Cancer, 129(8), 1183-1194. https://doi.org/10.1002/cncr.34655

Background: The routine assessment of progesterone receptor (PR) expression in breast cancer (BC) remains controversial. This study aimed to evaluate the role of PR expression in luminal BC, with emphasis on the definition of positivity and its progn... Read More about The clinical value of progesterone receptor expression in luminal breast cancer: A study of a large cohort with long-term follow-up.

The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer (2023)
Journal Article
Metzler, V. M., de Brot, S., Haigh, D. B., Woodcock, C. L., Lothion-Roy, J., Harris, A. E., …Jeyapalan, J. N. (2023). The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer. Frontiers in Cell and Developmental Biology, 11, Article 1116424. https://doi.org/10.3389/fcell.2023.1116424

Histone H3 lysine 4 (H3K4) methylation is key epigenetic mark associated with active transcription and is a substrate for the KDM1A/LSD1 and KDM5B/JARID1B lysine demethylases. Increased expression of KDM1A and KDM5B is implicated in many cancer types... Read More about The KDM5B and KDM1A lysine demethylases cooperate in regulating androgen receptor expression and signalling in prostate cancer.

Evolving DNA repair synthetic lethality targets in cancer (2022)
Journal Article
Kulkarni, S., Brownlie, J., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2022). Evolving DNA repair synthetic lethality targets in cancer. Bioscience Reports, 42(12), Article BSR20221713. https://doi.org/10.1042/BSR20221713

DNA damage signaling response and repair (DDR) is a critical defense mechanism against genomic instability. Impaired DNA repair capacity is an important risk factor for cancer development. On the other hand, up-regulation of DDR mechanisms is a featu... Read More about Evolving DNA repair synthetic lethality targets in cancer.

A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients (2022)
Journal Article
Xu, Q., Kaur, J., Wylie, D., Mittal, K., Li, H., Kolachina, R., …Aneja, R. (2022). A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients. International Journal of Molecular Sciences, 23(21), Article 13322. https://doi.org/10.3390/ijms232113322

Extensive intratumoral heterogeneity (ITH) is believed to contribute to therapeutic failure and tumor recurrence, as treatment-resistant cell clones can survive and expand. However, little is known about ITH in triple-negative breast cancer (TNBC) be... Read More about A Case Series Exploration of Multi-Regional Expression Heterogeneity in Triple-Negative Breast Cancer Patients.

Defining invasion in breast cancer: the role of basement membrane (2022)
Journal Article
Ghannam, S. F., Rutland, C. S., Allegrucci, C., Mongan, N. P., & Rakha, E. (2022). Defining invasion in breast cancer: the role of basement membrane. Journal of Clinical Pathology, https://doi.org/10.1136/jcp-2022-208584

Basement membrane (BM) is an amorphous, sheet-like structure separating the epithelium from the stroma. BM is characterised by a complex structure comprising collagenous and non-collagenous proteoglycans and glycoproteins. In the breast, the thicknes... Read More about Defining invasion in breast cancer: the role of basement membrane.

Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer (2022)
Journal Article
Harris, A. E., Metzler, V. M., Lothion-Roy, J., Varun, D., Woodcock, C. L., Haigh, D. B., …Jeyapalan, J. N. (2022). Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer. Frontiers in Endocrinology, 13, Article 1006101. https://doi.org/10.3389/fendo.2022.1006101

Androgen deprivation therapies (ADTs) are important treatments which inhibit androgen-induced prostate cancer (PCa) progression by either preventing androgen biosynthesis (e.g. abiraterone) or by antagonizing androgen receptor (AR) function (e.g. bic... Read More about Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.

The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer (2022)
Journal Article
Haigh, D. B., Woodcock, C. L., Lothion-Roy, J., Harris, A. E., Metzler, V. M., Persson, J. L., …Mongan, N. P. (2022). The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer. Cancers, 14(20), Article 5148. https://doi.org/10.3390/cancers14205148

Prostate cancer (PCa) is a leading cause of cancer-related deaths and is driven by aberrant androgen receptor (AR) signalling. For this reason, androgen deprivation therapies (ADTs) that suppress androgen-induced PCa progression either by preventing... Read More about The METTL3 RNA Methyltransferase Regulates Transcriptional Networks in Prostate Cancer.