All Outputs (48)

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., …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.

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., …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.

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.

Towards Personalized Management of Ovarian Cancer (2022)
Journal Article
Algethami, M., Kulkarni, S., Sadiq, M. T., Tang, H. K., Brownlie, J., Jeyapalan, J. N., …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., …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.

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., …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.

Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers (2021)
Journal Article
Ali, R., Alabdullah, M., Algethami, M., Alblihy, A., Miligy, I., Shoqafi, A., …Madhusudan, S. (2021). Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers. Theranostics, 11(17), 8350-8361. https://doi.org/10.7150/thno.51456

Rationale: The human ligases (LIG1, LIG3 and LIG4) are essential for the maintenance of genomic integrity by catalysing the formation of phosphodiester bonds between adjacent 5'-phosphoryl and 3'-hydroxyl termini at single and double strand breaks in... Read More about Ligase 1 is a predictor of platinum resistance and its blockade is synthetically lethal in XRCC1 deficient epithelial ovarian cancers.

Genome-Wide Analysis Unveils DNA Helicase RECQ1 as a Regulator of Estrogen Response Pathway in Breast Cancer Cells (2021)
Journal Article
Lu, X., Redon, C. E., Tang, W., Parvathaneni, S., Bokhari, B., Debnath, S., …Sharma, S. (2021). Genome-Wide Analysis Unveils DNA Helicase RECQ1 as a Regulator of Estrogen Response Pathway in Breast Cancer Cells. Molecular and Cellular Biology, 41(4), e00515-20. https://doi.org/10.1128/mcb.00515-20

Susceptibility to breast cancer is significantly increased in individuals with germ line mutations in RECQ1 (also known as RECQL or RECQL1), a gene encoding a DNA helicase essential for genome maintenance. We previously reported that RECQ1 expression... Read More about Genome-Wide Analysis Unveils DNA Helicase RECQ1 as a Regulator of Estrogen Response Pathway in Breast Cancer Cells.

Clinicopathological and Functional Evaluation Reveal NBS1 as a Predictor of Platinum Resistance in Epithelial Ovarian Cancers (2021)
Journal Article
Alblihy, A., Alabdullah, M. L., Ali, R., Algethami, M., Toss, M. S., Mongan, N. P., …Madhusudan, S. (2021). Clinicopathological and Functional Evaluation Reveal NBS1 as a Predictor of Platinum Resistance in Epithelial Ovarian Cancers. Biomedicines, 9(1), Article 56. https://doi.org/10.3390/biomedicines9010056

Platinum resistance seriously impacts on the survival outcomes of patients with ovarian cancers. Platinum-induced DNA damage is processed through DNA repair. NBS1 is a key DNA repair protein. Here, we evaluated the role of NBS1 in ovarian cancers. NB... Read More about Clinicopathological and Functional Evaluation Reveal NBS1 as a Predictor of Platinum Resistance in Epithelial Ovarian Cancers.

RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers (2020)
Journal Article
Alblihy, A., Alabdullah, M. L., Toss, M. S., Algethami, M., Mongan, N. P., Rakha, E. A., & Madhusudan, S. (2020). RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers. Molecular Biomedicine, 1(1), Article 19. https://doi.org/10.1186/s43556-020-00023-y

Intrinsic or acquired resistance seriously limits the use of platinating agents in advanced epithelial ovarian cancers. Increased DNA repair capacity is a key route to platinum resistance. RAD50 is a critical component of the MRN complex, a ‘first re... Read More about RAD50 deficiency is a predictor of platinum sensitivity in sporadic epithelial ovarian cancers.

Werner Syndrome Protein Expression in Breast Cancer (2020)
Journal Article
Savva, C., Sadiq, M., Sheikh, O., Karim, S., Trivedi, S., Green, A. R., …Arora, A. (2021). Werner Syndrome Protein Expression in Breast Cancer. Clinical Breast Cancer, 21(1), 57-73.E7. https://doi.org/10.1016/j.clbc.2020.07.013

Introduction Werner protein (WRN) plays an important role in DNA repair, replication, transcription, and consequently genomic stability via its DNA-helicase and exonuclease activity. Loss of function of WRN is associated with Werner syndrome (WS), w... Read More about Werner Syndrome Protein Expression in Breast Cancer.

PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers (2019)
Journal Article
Mesquita, K. A., Ali, R., Chan, S. Y., Alabdullah, M., Alblihy, A., Miligy, I., …Madhusudan, S. (2020). PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers. Cancer Letters, 469, 124-133. https://doi.org/10.1016/j.canlet.2019.10.035

© 2019 Elsevier B.V. PARP1 inhibitor (Niraparib, Olaparib, Rucaparib) maintenance therapy improves progression-free survival in platinum sensitive sporadic epithelial ovarian cancers. However, biomarkers of response to PARPi therapy is yet to be clea... Read More about PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers.

ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85α Deficient Cancer Cells and Influence Platinum Sensitivity (2019)
Journal Article
Ali, R., Alabdullah, M., Miligy, I., Normatova, M., Babaei-Jadidi, R., S. Nateri, A., …Madhusudan, S. (2019). ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85α Deficient Cancer Cells and Influence Platinum Sensitivity. Cells, 8(10), Article 1271. https://doi.org/10.3390/cells8101271

Ataxia-telegiectasia mutated (ATM), phosphatase and tensin homolog (PTEN), and p85α are key tumour suppressors. Whether ATM regulates PTEN expression and influence platinum sensitivity is unknown. We generated ATM knockdowns (KD) and CRISPR knock out... Read More about ATM Regulated PTEN Degradation Is XIAP E3 Ubiquitin Ligase Mediated in p85α Deficient Cancer Cells and Influence Platinum Sensitivity.

Upper GI biopsies for adenocarcinoma: how many biopsies should endoscopists take? (2018)
Journal Article
Kaye, P., Lindsay, D., Madhusudan, S., Vohra, R., Catton, J., Platt, C., & Ragunath, K. (2019). Upper GI biopsies for adenocarcinoma: how many biopsies should endoscopists take?. Histopathology, 74(6), 959-963. https://doi.org/10.1111/his.13816

Aims: There is evidence that 4 or 5 gastric cancer biopsies are required for accurate HER2 interpretation. However, the number of biopsies that need to be taken to reach this number of viable cancer biopsies is without evidence. This study aimed to a... Read More about Upper GI biopsies for adenocarcinoma: how many biopsies should endoscopists take?.

LY2495655, an antimyostatin antibody in pancreatic cancer: a randomized phase 2 trial (2018)
Journal Article
Golan, T., Geva, R., Richards, D., Madhusudan, S., Lin, B. K., Wang, H. T., …Stemmer, S. M. (2018). LY2495655, an antimyostatin antibody in pancreatic cancer: a randomized phase 2 trial. Journal of Cachexia, Sarcopenia and Muscle, 9(5), 871-879. https://doi.org/10.1002/jcsm.12331

Background: Cachexia is a formidable clinical challenge in pancreatic cancer. We assessed LY2495655 (antimyostatin antibody) plus standard-of-care chemotherapy in pancreatic cancer using cachexia status as a stratifier. Methods: In this randomize... Read More about LY2495655, an antimyostatin antibody in pancreatic cancer: a randomized phase 2 trial.

Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial (2018)
Journal Article
Backen, A. C., Lopes, A., Wasan, H., Palmer, D. H., Duggan, M., Cunningham, D., …Valle, J. W. (2018). Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. British Journal of Cancer, 119(1), 27-35. https://doi.org/10.1038/s41416-018-0132-8

BACKGROUND: Advanced biliary tract cancer (ABC) has a poor prognosis. Cediranib, in addition to cisplatin/gemcitabine [CisGem], improved the response rate, but did not improve the progression-free survival (PFS) in the ABC-03 study. Minimally invasiv... Read More about Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial.

Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer (2017)
Journal Article
Naidoo, K., Wai, P. T., Maguire, S. L., Daley, F., Haider, S., Kriplani, D., …Natrajan, R. (2018). Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer. Molecular Cancer Therapeutics, 17(1), 306-315. https://doi.org/10.1158/1535-7163.mct-17-0760

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. We therefore aimed to assess t... Read More about Evaluation of CDK12 protein expression as a potential novel biomarker for DNA damage response–targeted therapies in breast cancer.

RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner (2017)
Journal Article
Parvathaneni, S., Lu, X., Choudhary, R., Lal, A., Madhusudan, S., & Sharma, S. (2017). RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner. Oncotarget, https://doi.org/10.18632/oncotarget.18237

Sensitivity of cancer cells to DNA damaging chemotherapeutics is determined by DNA repair processes. Consequently, cancer cells may upregulate the expression of certain DNA repair genes as a mechanism to promote chemoresistance. Here, we report tha... Read More about RECQ1 expression is upregulated in response to DNA damage and in a p53-dependent manner.