Professor SRINIVASAN MADHUSUDAN's Outputs (81)

The role of the ALKBH5 RNA demethylase in invasive breast cancer (2024)
Journal Article
Woodcock, C. L., Alsaleem, M., Toss, M. S., Lothion-Roy, J., Harris, A. E., Jeyapalan, J. N., Blatt, N., Rizvanov, A. A., Miftakhova, R. R., Kariri, Y. A., Madhusudan, S., Green, A. R., Rutland, C. S., Fray, R. G., Rakha, E. A., & Mongan, N. P. (2024). The role of the ALKBH5 RNA demethylase in invasive breast cancer. Discover Oncology, 15(1), Article 343. https://doi.org/10.1007/s12672-024-01205-8

Background: N6-methyladenosine (m6A) is the most common internal RNA modification and is involved in regulation of RNA and protein expression. AlkB family member 5 (ALKBH5) is a m6A demethylase. Given the important role of m6A in biological mechanism... Read More about The role of the ALKBH5 RNA demethylase in invasive breast cancer.

Epitranscriptomic mechanisms of androgen signalling and prostate cancer (2024)
Journal Article
Patke, R., Harris, A. E., Woodcock, C. L., Thompson, R., Santos, R., Kumari, A., Allegrucci, C., Archer, N., Gudas, L. J., Robinson, B. D., Persson, J. L., Fray, R., Jeyapalan, J., Rutland, C. S., Rakha, E., Madhusudan, S., Emes, R. D., Muyangwa-Semenova, M., Alsaleem, M., de Brot, S., …Lothion-Roy, J. (2024). Epitranscriptomic mechanisms of androgen signalling and prostate cancer. Neoplasia, 56, Article 101032. https://doi.org/10.1016/j.neo.2024.101032

Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen... Read More about Epitranscriptomic mechanisms of androgen signalling and prostate cancer.

The characteristics and prognostic significance of histone H1 expression in breast cancer (2024)
Journal Article
Lashen, A. G., Almalki, N., Toss, M., Mirza, S., Malki, M. I., Rutland, C. S., Jeyapalan, J. N., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. A. (2024). The characteristics and prognostic significance of histone H1 expression in breast cancer. Pathology, 56(6), 826-833. https://doi.org/10.1016/j.pathol.2024.03.012

Histone H1 (H.H1) is involved in chromatin organisation and gene regulation and is overexpressed in many malignant tumours, including breast cancer (BC). This study proposed and evaluated the prognostic role of H.H1 expression in BC.

H.H1 mRNA exp... Read More about The characteristics and prognostic significance of histone H1 expression in breast cancer.

Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers (2024)
Journal Article
Lashen, A., Alqahtani, S., Shoqafi, A., Algethami, M., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2024). Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers. International Journal of Molecular Sciences, 25(9), Article 5053. https://doi.org/10.3390/ijms25095053

Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largel... Read More about Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.

The Clinicopathological Significance of the Cyclin D1/E1–Cyclin-Dependent Kinase (CDK2/4/6)–Retinoblastoma (RB1/pRB1) Pathway in Epithelial Ovarian Cancers (2024)
Journal Article
Lashen, A., Algethami, M., Alqahtani, S., Shoqafi, A., Sheha, A., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2024). The Clinicopathological Significance of the Cyclin D1/E1–Cyclin-Dependent Kinase (CDK2/4/6)–Retinoblastoma (RB1/pRB1) Pathway in Epithelial Ovarian Cancers. International Journal of Molecular Sciences, 25(7), Article 4060. https://doi.org/10.3390/ijms25074060

Cyclin-dependent kinases (CDK2, CDK4, CDK6), cyclin D1, cyclin E1 and phosphorylated retinoblastoma (pRB1) are key regulators of the G1/S cell cycle checkpoint and may influence platinum response in ovarian cancers. CDK2/4/6 inhibitors are emerging t... Read More about The Clinicopathological Significance of the Cyclin D1/E1–Cyclin-Dependent Kinase (CDK2/4/6)–Retinoblastoma (RB1/pRB1) Pathway in Epithelial Ovarian Cancers.

Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite (2023)
Journal Article
Ali, R., Alhaj Sulaiman, A., Memon, B., Pradhan, S., Algethami, M., Aouida, M., McKay, G., Madhusudan, S., Abdelalim, E. M., & Ramotar, D. (2023). Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite. Cells, 12(23), Article 2682. https://doi.org/10.3390/cells12232682

Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of... Read More about Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite.

Clinical Impact of CDK4/6 Inhibitors in De Novo or PR− or Very Elderly Post-Menopausal ER+/HER2− Advanced Breast Cancers (2023)
Journal Article
Tang, H., Yeo, D., De Souza, K., Ahmad, O., Shafiq, T., Ofor, O., Anand, A., Karim, S., Khan, S., & Madhusudan, S. (2023). Clinical Impact of CDK4/6 Inhibitors in De Novo or PR− or Very Elderly Post-Menopausal ER+/HER2− Advanced Breast Cancers. Cancers, 15(21), Article 5164. https://doi.org/10.3390/cancers15215164

The CDK4/6 inhibitors significantly increase progression-free survival (PFS) in ER+/HER2− advanced breast cancer patients. In clinical trials, overall survival (OS) improvement has been demonstrated for ribociclib and abemaciclib but not for palbocic... Read More about Clinical Impact of CDK4/6 Inhibitors in De Novo or PR− or Very Elderly Post-Menopausal ER+/HER2− Advanced Breast Cancers.

Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer (2023)
Journal Article
Lashen, A. G., Toss, M. S., Wootton, L., Green, A. R., Mongan, N. P., Madhusudan, S., & Rakha, E. (2023). Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer. Histopathology, 83(3), 414-425. https://doi.org/10.1111/his.14960

Background: Polo-like kinase-1 (PLK1) plays a crucial role in cell cycle progression,and it is considered a potential therapeutic target in many cancers. Although the role of PLK1 is well established in triple negative breast cancer (TNBC) as an onco... Read More about Characteristics and prognostic significance of polo-like kinase-1 (PLK1) expression in breast cancer.

Targeting DNA damage repair precision medicine strategies in cancer (2023)
Journal Article
Brownlie, J., Kulkarni, S., Algethami, M., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2023). Targeting DNA damage repair precision medicine strategies in cancer. Current Opinion in Pharmacology, 70, Article 102381. https://doi.org/10.1016/j.coph.2023.102381

DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as plati... Read More about Targeting DNA damage repair precision medicine strategies in cancer.

Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers (2023)
Journal Article
Algethami, M., Toss, M. S., Woodcock, C. L., Jaipal, C., Brownlie, J., Shoqafi, A., Alblihy, A., Mesquita, K. A., Green, A. R., Mongan, N. P., Jeyapalan, J. N., Rakha, E. A., & Madhusudan, S. (2023). Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers. npj Breast Cancer, 9, Article 18. https://doi.org/10.1038/s41523-023-00524-3

Replication Protein A (RPA), a heterotrimeric complex consisting of RPA1, 2, and 3 subunits, is a single-stranded DNA (ssDNA)-binding protein that is critically involved in replication, checkpoint regulation and DNA repair. Here we have evaluated RPA... Read More about Unravelling the clinicopathological and functional significance of replication protein A (RPA) heterotrimeric complex in breast cancers.

Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer (2023)
Journal Article
Lothion-Roy, J., Haigh, D. B., Harris, A. E., Metzler, V. M., Alsaleem, M., Toss, M. S., Kariri, Y., Ntekim, A., Robinson, B. D., Khani, F., Gudas, L. J., Allegrucci, C., James, V. H., Madhusudan, S., Mather, M., Emes, R. D., Archer, N., Fray, R. G., Rakha, E., Jeyapalan, J. N., …Woodcock, C. L. (2023). Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer. Frontiers in Genetics, 13, Article 1096071. https://doi.org/10.3389/fgene.2022.1096071

N6-methyladenosine (m6A) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the m6A modification. These proteins, and the m6A modification, are... Read More about Clinical and molecular significance of the RNA m6A methyltransferase complex in prostate cancer.

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., Nilsson, E. M., Ntekim, A., Persson, J. L., Robinson, B. D., Khani, F., Laursen, K. B., Gudas, L. J., Toss, M. S., Madhusudan, S., Rakha, E., Heery, D. M., Rutland, C. S., Mongan, N. P., & 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.

Towards Personalized Management of Ovarian Cancer (2022)
Journal Article
Algethami, M., Kulkarni, S., Sadiq, M. T., Tang, H. K., Brownlie, J., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2022). Towards Personalized Management of Ovarian Cancer. Cancer Management and Research, 14, 3469-3483. https://doi.org/10.2147/CMAR.S366681

Despite advances in surgery and chemotherapy, the overall outcomes for patients with advanced ovarian cancer remain poor. Although initial response rates to platinum-based chemotherapy is about 60–80%, most patients will have recurrence and succumb t... Read More about Towards Personalized Management of Ovarian 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.

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., Endeley, C., Haque, M., Toss, M. S., Alsaleem, M., Persson, J. L., Gudas, L. J., Rakha, E., Robinson, B. D., Khani, F., Martin, L. M., Moyer, J. E., Brownlie, J., Madhusudan, S., Allegrucci, C., …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., Robinson, B. D., Khani, F., Alsaleem, M., Ntekim, A., Madhusudan, S., Davis, M. B., Laursen, K. B., Gudas, L. J., Rutland, C. S., Toss, M. S., Archer, N., Bodi, Z., Rakha, E. A., Fray, R. G., …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.

The Blursday database as a resource to study subjective temporalities during COVID-19 (2022)
Journal Article
Chaumon, M., Rioux, P.-A., Herbst, S. K., Spiousas, I., Kübel, S. L., Gallego Hiroyasu, E. M., Runyun, Ş. L., Micillo, L., Thanopoulos, V., Mendoza-Duran, E., Wagelmans, A., Mudumba, R., Tachmatzidou, O., Cellini, N., D’Argembeau, A., Giersch, A., Grondin, S., Gronfier, C., Igarzábal, F. A., Klarsfeld, A., …van Wassenhove, V. (2022). The Blursday database as a resource to study subjective temporalities during COVID-19. Nature Human Behaviour, 6, 1587-1599. https://doi.org/10.1038/s41562-022-01419-2

The COVID-19 pandemic and associated lockdowns triggered worldwide changes in the daily routines of human experience. The Blursday database provides repeated measures of subjective time and related processes from participants in nine countries tested... Read More about The Blursday database as a resource to study subjective temporalities during COVID-19.

Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers (2022)
Journal Article
Alblihy, A., Ali, R., Algethami, M., Shoqafi, A., Toss, M. S., Brownlie, J., Tatum, N. J., Hickson, I., Moran, P. O., Grabowska, A., Jeyapalan, J. N., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2022). Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers. npj Precision Oncology, 6(1), https://doi.org/10.1038/s41698-022-00298-0

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have... Read More about Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.

Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers (2021)
Journal Article
Alblihy, A., Shoqafi, A., Toss, M. S., Algethami, M., Harris, A. E., Jeyapalan, J. N., Abdel-Fatah, T., Servante, J., Chan, S. Y., Green, A., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2021). Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers. npj Breast Cancer, 7(1), 1-10. https://doi.org/10.1038/s41523-021-00350-5

The MRE11–RAD50–NBS1 (MRN) complex is critical for genomic stability. Although germline mutations in MRN may increase breast cancer susceptibility, such mutations are extremely rare. Here, we have conducted a comprehensive clinicopathological study o... Read More about Untangling the clinicopathological significance of MRE11-RAD50-NBS1 complex in sporadic breast cancers.

The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS) (2021)
Journal Article
Al-Kawaz, A., Ali, R., Toss, M. S., Miligy, I. M., Mohammed, O. J., Green, A. R., Madhusudan, S., & Rakha, E. A. (2021). The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS). Breast Cancer Research and Treatment, 190, 39-51. https://doi.org/10.1007/s10549-021-06357-7

Background: The prediction of clinical behaviour of breast ductal carcinoma in situ (DCIS) and its progression to invasive disease remains a challenge. Alterations of DNA damage repair mechanisms are associated with invasive breast cancer (BC). This... Read More about The frequency and clinical significance of DNA polymerase beta (POLβ) expression in breast ductal carcinoma in situ (DCIS).