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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., …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., …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., …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., …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., …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.

The Blursday database as a resource to study subjective temporalities during COVID-19 (2022)
Journal Article
Chaumon, M., Rioux, P., Herbst, S. K., Spiousas, I., Kübel, S. L., Gallego Hiroyasu, E. M., …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., …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., …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., …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).

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.

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ (2021)
Journal Article
Al-Kawaz, A., Miligy, I. M., Toss, M. S., Mohammed, O. J., Green, A. R., Madhusudan, S., & Rakha, E. A. (2021). The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ. Breast Cancer Research and Treatment, 188(1), 53-63. https://doi.org/10.1007/s10549-021-06271-y

Background Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast c... Read More about The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ.

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.

XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib (2020)
Journal Article
Ali, R., Alblihy, A., Toss, M. S., Algethami, M., Al Sunni, R., Green, A. R., …Madhusudan, S. (2020). XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib. Therapeutic Advances in Medical Oncology, 12, 175883592097420. https://doi.org/10.1177/1758835920974201

Background: PARP inhibitor (PARPi) monotherapy is a new strategy in BRCA germ-line deficient triple negative breast cancer (TNBC). However, not all patients respond, and the development of resistance limits the use of PARPi monotherapy. Therefore, th... Read More about XRCC1 deficient triple negative breast cancers are sensitive to ATR, ATM and Wee1 inhibitor either alone or in combination with olaparib.

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 p85? 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 p85? 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 p85? Deficient Cancer Cells and Influence Platinum Sensitivity.

ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers (2019)
Journal Article
Abdel-Fatah, T. M., Ali, R., Sadiq, M., Moseley, P. M., Mesquita, K. A., Ball, G., …Madhusudan, S. (2019). ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers. Cancers, 11(8), Article 1149. https://doi.org/10.3390/cancers11081149

Genomic instability could be a beneficial predictor for anthracycline or taxane chemotherapy. We interrogated 188 DNA repair genes in the METABRIC cohort (n = 1980) to identify genes that influence overall survival (OS). We then evaluated the clinico... Read More about ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers.

Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers (2019)
Journal Article
Savva, C., De Souza, K., Ali, R., Rakha, E. A., Green, A. R., & Madhusudan, S. (2019). Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers. Breast Cancer Research and Treatment, 175(1), 105–115. https://doi.org/10.1007/s10549-018-05113-8

Purpose: MYC transcription factor has critical roles in cell growth, proliferation, metabolism, differentiation, transformation and angiogenesis. MYC overexpression is seen in about 15% of breast cancers and linked to aggressive phenotypes. MYC overe... Read More about Clinicopathological significance of ataxia-telangiectasia-mutated (ATM) kinase and ataxia telangiectasia-mutated and Rad3 related (ATR) kinase in MYC overexpressed breast cancers.

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?.

Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention (2018)
Journal Article
Ali, R., Al-Kawaz, A., Toss, M. S., Green, A. R., Miligy, I. M., Mesquita, K. A., …Madhusudan, S. (2018). Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention. Cancer Research, 78(24), 6818-6827. https://doi.org/10.1158/0008-5472.CAN-18-0633

© 2018 American Association for Cancer Research. Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may resu... Read More about Targeting PARP1 in XRCC1-deficient sporadic invasive breast cancer or preinvasive ductal carcinoma in situ induces synthetic lethality and chemoprevention.

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.

The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response (2018)
Journal Article
Barone, G., Arora, A., Ganesh, A., Abdel-Fatah, T., Moseley, P., Ali, R., …Collis, S. J. (2018). The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response. Oncotarget, 9, 29508-29524. https://doi.org/10.18632/oncotarget.25686

Background: Cyclin-Dependent Kinases (CDKs) are established anti-cancer drug targets and a new generation of CDK inhibitors are providing clinical benefits to a sub-set of breast cancer patients. We have recently shown that human CDK18 promotes effic... Read More about The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response.

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. (in press). Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial. British Journal of Cancer, 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.

Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy (2018)
Journal Article
Al-Subhi, N., Ali, R., Abdel-Fatah, T., Moseley, P. M., Chan, S. Y., Green, A. R., …Madhusudan, S. (2018). Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy. Breast Cancer Research and Treatment, 169(2), 277–286. https://doi.org/10.1007/s10549-018-4683-4

Purpose: PTEN, a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in P... Read More about Targeting ataxia telangiectasia mutated and Rad3 related kinase (ATR) in PTEN deficient breast cancers for personalized therapy.

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.

Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers (2017)
Journal Article
Green, A. R., Aleskandarany, M. A., Ali, R., Hodgson, E. G., Atabani, S., De Souza, K., …Madhusudan, S. (2017). Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers. Cancer Immunology Research, 5(4), 292-299. https://doi.org/10.1158/2326-6066.CIR-16-0195

© 2017 American Association for Cancer Research. Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand br... Read More about Clinical impact of tumor DNA repair expression and T-cell infiltration in breast cancers.

Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial (2017)
Journal Article
Middleton, G., Palmer, D. H., Greenhalf, W., Ghaneh, P., Jackson, R., Cox, T., …Neoptolemos, J. P. (2017). Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. Lancet Oncology, 18(4), 486-499. https://doi.org/10.1016/S1470-2045%2817%2930084-0

Methods: The Vandetanib in Pancreatic Cancer (ViP) trial was a phase 2 double-blind, multicentre, randomised placebo-controlled trial in previously untreated adult patients (aged ≥18 years) diagnosed with locally advanced or metastatic carcinoma of t... Read More about Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial.

DNA damage repair in breast cancer and its therapeutic implications (2016)
Journal Article
Ali, R., Rakha, E. A., Madhusudan, S., & Bryant, H. E. (2017). DNA damage repair in breast cancer and its therapeutic implications. Pathology, 49(2), 156-165. doi:10.1016/j.pathol.2016.11.002

The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in t... Read More about DNA damage repair in breast cancer and its therapeutic implications.

Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers (2016)
Journal Article
Arora, A., Parvathaneni, S., Aleskandarany, M. A., Agarwal, D., Ali, R., Abdel-Fatah, T., …Madhusudan, S. (2017). Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers. Molecular Cancer Therapeutics, 16(1), https://doi.org/10.1158/1535-7163.MCT-16-0290

RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1... Read More about Clinicopathological and functional significance of RECQL1 helicase in sporadic breast cancers.

The Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma (2016)
Journal Article
Rollins, K. E., Tewari, N., Ackner, A., Awwad, A., Madhusudan, S., Macdonald, I. A., …Lobo, D. N. (2016). The Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma. Clinical Nutrition, 35(5), 1103-1109. https://doi.org/10.1016/j.clnu.2015.08.005

Abstract Background and aims: Patients with pancreatic cancer have a poor prognosis, are often cachectic, and frequently demonstrate features of systemic inflammation, which may contribute to the phenomenon of myosteatosis. Analysis of body compos... Read More about The Impact of Sarcopenia and Myosteatosis on Outcomes of Unresectable Pancreatic Cancer or Distal 1 Cholangiocarcinoma.

Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein (2016)
Journal Article
Alshareeda, A., Negm, O. H., Aleskandarany, M. A., Green, A. R., Nolan, C., Tighe, P. J., …Rakha, E. (2016). Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein. Breast Cancer Research and Treatment, 159(1), 41-53. https://doi.org/10.1007/s10549-016-3915-8

Impaired DNA damage response (DDR) may play a fundamental role in the pathogenesis of breast cancer (BC). RAD51 is a key player in DNA double-strand break repair. In this study, we aimed to assess the biological and clinical significance of RAD51 exp... Read More about Clinical and biological significance of RAD51 expression in breast cancer: a key DNA damage response protein.

Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway (2016)
Journal Article
Mo, D., Fang, H., Niu, K., Liu, J., Wu, M., Li, S., …Zhao, Y. (2016). Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway. Cancer Research, 76(10), https://doi.org/10.1158/0008-5472.CAN-15-2361

Elevation of the DNA-unwinding helicase RECQL4, which participates in various DNA repair pathways, has been suggested to contribute to the pathogenicity of various human cancers, including gastric cancer. In this study, we addressed the prognostic an... Read More about Human helicase RECQL4 drives cisplatin resistance in gastric cancer by activating an AKT-YB1-MDR1 signaling pathway.

MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours (2016)
Journal Article
Green, A. R., Aleskandarany, M. A., Agarwal, D., Elsheikh, S., Nolan, C. C., Diez-Rodriguez, M., …Rakha, E. A. (2016). MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours. British Journal of Cancer, 114(8), 917-928. https://doi.org/10.1038/bjc.2016.46

Background: MYC is amplified in approximately 15% of breast cancers (BCs) and is associated with poor outcome. c-MYC protein is multi-faceted and participates in many aspects of cellular function and is linked with therapeutic response in BCs. We... Read More about MYC functions are specific in biological subtypes of breast cancer and confers resistance to endocrine therapy in luminal tumours.

Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer (2016)
Journal Article
Shamanna, R. A., Lu, H., Croteau, D. L., Arora, A., Agarwal, D., Ball, G., …Bohr, V. A. (2016). Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer. Oncotarget, 7(12), 13269-13284. https://doi.org/10.18632/oncotarget.7906

Werner syndrome protein (WRN) is a RecQ helicase that participates in DNA repair, genome stability and cellular senescence. The five human RecQ helicases, RECQL1, Bloom, WRN, RECQL4 and RECQL5 play critical roles in DNA repair and cell survival after... Read More about Camptothecin targets WRN protein: mechanism and relevance in clinical breast cancer.

RECQL4 helicase has oncogenic potential in sporadic breast cancers (2016)
Journal Article
Arora, A., Agarwal, D., Abdel-Fatah, T. M., Lu, H., Croteau, D. L., Moseley, P., …Madhusudan, S. (2016). RECQL4 helicase has oncogenic potential in sporadic breast cancers. Journal of Pathology, 238(4), 495-501. https://doi.org/10.1002/path.4681

RECQL4 helicase is a molecular motor that unwinds DNA, a process essential during DNA replication and DNA repair. Germ-line mutations in RECQL4 cause type II Rothmund–Thomson syndrome (RTS), characterized by a premature ageing phenotype and cancer pr... Read More about RECQL4 helicase has oncogenic potential in sporadic breast cancers.

Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers (2015)
Journal Article
Arora, A., Abdel-Fatah, T. M., Agarwal, D., Doherty, R., Croteau, D. L., Moseley, P. M., …Madhusudan, S. (2016). Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers. Carcinogenesis, 37(1), 63-71. https://doi.org/10.1093/carcin/bgv163

RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In this... Read More about Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers.

Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer (2015)
Journal Article
Alsubhi, N., Middleton, F., Abdel-Fatah, T. M., Stephens, P., Doherty, R., Arora, A., …Madhusudan, S. (2016). Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer. Molecular Oncology, 10(2), 213-223. https://doi.org/10.1016/j.molonc.2015.09.009

Radiation?induced DNA damage activates the DNA damage response (DDR). DDR up?regulation may predict radio?resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancer... Read More about Chk1 phosphorylated at serine345 is a predictor of early local recurrence and radio-resistance in breast cancer.

Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial (2015)
Journal Article
Valle, J. W., Wasan, H., Lopes, A., Backen, A. C., Palmer, D. H., Morris, K., …Bridgewater, J. A. (2015). Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial. Lancet Oncology, 16(8), https://doi.org/10.1016/S1470-2045%2815%2900139-4

BACKGROUND: Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addi... Read More about Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial.

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.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer (2015)
Journal Article
Alshareeda, A., Negm, O., Green, A., Nolan, C., Tighe, P., Albarakati, N., …Rakha, E. (2015). KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer. British Journal of Cancer, 112(12), 1929–1937. https://doi.org/10.1038/bjc.2015.165

Background: It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) prote... Read More about KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity (2015)
Journal Article
Chua, J., Vankemmelbeke, M., McIntosh, R. S., Clarke, P. A., Moss, R., Parsons, T., …Durrant, L. (2015). Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity. Clinical Cancer Research, 21(13), 2963-2974. https://doi.org/10.1158/1078-0432.CCR-14-3030

© 2015 American Association for Cancer Research. Purpose: To produce antitumor monoclonal antibodies (mAbs) targeting glycans as they are aberrantly expressed in tumors and are coaccessory molecules for key survival pathways. Experimental Design: Two... Read More about Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity.

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.

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.

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.

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?.

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy (2014)
Journal Article
Albarakati, N., Abdel-Fatah, T. M., Doherty, R., Russell, R., Agarwal, D., Moseley, P., …Madhusudan, S. (2015). Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy. Molecular Oncology, 9(1), 204-217. https://doi.org/10.1016/j.molonc.2014.08.001

BRCA1, a key factor in homologous recombination (HR) repair may also regulate base excision repair (BER). Targeting BRCA1?BER deficient cells by blockade of ATM and DNA?PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1... Read More about Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy.

Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era (2014)
Journal Article
Perry, C., Agarwal, D., Abdel-Fatah, T. M., Lourdusamy, A., Grundy, R., Auer, D. T., …Madhusudan, S. (2014). Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era. Oncotarget, 5(14), 5764-5781. https://doi.org/10.18632/oncotarget.2180

Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Ca... Read More about Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era.

Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers (2014)
Journal Article
Abdel-Fatah, T., Arora, A., Agarwal, D., Moseley, P., Perry, C., Thompson, N., …Madhusudan, S. (2014). Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers. Breast Cancer Research and Treatment, 146(2), 309-320. https://doi.org/10.1007/s10549-014-3035-2

DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a serine threonine kinase belonging to the PIKK family (phosphoinositide 3-kinase-like-family of protein kinase), is a critical component of the non-homologous end-joining pathway required fo... Read More about Adverse prognostic and predictive significance of low DNA-dependent protein kinase catalytic subunit (DNA-PKcs) expression in early-stage breast cancers.

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial (2014)
Journal Article
Middleton, G., Silcocks, P., Cox, T., Valle, J., Wadsley, J., Propper, D., …Neoptolemos, J. P. (2014). Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncology, 15(8), https://doi.org/10.1016/S1470-2045%2814%2970236-0

BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer. METHODS: TeloVac was a three-g... Read More about Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer (2014)
Journal Article
Abdel-Fatah, T. M., Russell, R., Albarakati, N., Maloney, D. J., Dorjsuren, D., Rueda, O. M., …Madhusudan, S. (2014). Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer. Molecular Oncology, 8(7), 1326-1338. https://doi.org/10.1016/j.molonc.2014.04.009

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and ha... Read More about Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer.

Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy (2014)
Journal Article
Abbotts, R., Jewell, R., Nsengimana, J., Maloney, D. J., Simeonov, A., Seedhouse, C., …Madhusudan, S. (2014). Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy. Oncotarget, 5(10), 3273-3286. https://doi.org/10.18632/oncotarget.1926

Phosphatase and tensin homolog (PTEN) loss is associated with genomic instability. APE1 is a key player in DNA base excision repair (BER) and an emerging drug target in cancer. We have developed small molecule inhibitors against APE1 repair nuclease... Read More about Targeting human apurinic/apyrimidinic endonuclease 1 (APE1) in phosphatase and tensin homolog (PTEN) deficient melanoma cells for personalized therapy.

SUMOylation proteins in breast cancer (2014)
Journal Article
Alshareeda, A. T., Negm, O. H., Green, A. R., Nolan, C., Tighe, P., Albarakati, N., …Rakha, E. A. (2014). SUMOylation proteins in breast cancer. Breast Cancer Research and Treatment, 144(3), 519-530. https://doi.org/10.1007/s10549-014-2897-7

Small Ubiquitin-like Modifier proteins (or SUMO) modify the function of protein substrates involved in various cellular processes including DNA damage response (DDR). It is becoming apparent that dysregulated SUMO contribute to carcinogenesis by affe... Read More about SUMOylation proteins in breast cancer.

DNA repair in cancer: emerging targets for personalized therapy (2014)
Journal Article
Abbotts, R., Thompson, N., & Madhusudan, S. (2014). DNA repair in cancer: emerging targets for personalized therapy. Breast Cancer: Targets and Therapy, 2014(6), https://doi.org/10.2147/CMAR.S50497

Genomic deoxyribonucleic acid (DNA) is under constant threat from endogenous and exogenous DNA damaging agents. Mammalian cells have evolved highly conserved DNA repair machinery to process DNA damage and maintain genomic integrity. Impaired DNA repa... Read More about DNA repair in cancer: emerging targets for personalized therapy.

DNA polymerase ? deficiency is linked to aggressive breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts (2014)
Journal Article
Abdel-Fatah, T. M., Russell, R., Agarwal, D., Moseley, P., Abayomi, M. A., Perry, C., …Madhusudan, S. (2014). DNA polymerase β deficiency is linked to aggressive breast cancer: A comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts. Molecular Oncology, 8(3), 520-532. https://doi.org/10.1016/j.molonc.2014.01.001

Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer (2014)
Journal Article
Abdel-Fatah, T. M. A., Perry, C., Moseley, P., Johnson, K., Arora, A., Chan, S., …Madhusudan, S. (2014). Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer. Breast Cancer Research and Treatment, 143(3), 411-421. https://doi.org/10.1007/s10549-013-2820-7

Oestrogen metabolites can induce oxidative DNA base damage and generate potentially mutagenic apurinic sites (AP sites) in the genomic DNA. If unrepaired, mutagenic AP sites could drive breast cancer pathogenesis and aggressive phenotypes. Human apur... Read More about Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer.

Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial (2013)
Journal Article
Ford, H., Marshall, A., Bridgewater, J. A., Janowitz, T., Coxon, F., Wadsley, J., …Dunn, J. A. (2014). Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncology, 15(1), https://doi.org/10.1016/S1470-2045%2813%2970549-7

BACKGROUND: Second-line chemotherapy for patients with oesophagogastric adenocarcinoma refractory to platinum and fluoropyrimidines has not shown benefits in health-related quality of life (HRQoL). We assessed whether the addition of docetaxel to act... Read More about Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial.

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays (2013)
Journal Article
Tewari, N., Zaitoun, A. M., Arora, A., Madhusudan, S., Ilyas, M., & Lobo, D. N. (2013). The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays. BMC Cancer, 13, Article 436. https://doi.org/10.1186/1471-2407-13-436

Background Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma.... Read More about The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays.

Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer? (2013)
Journal Article
Abdel-Fatah, T., Arora, A., Gorguc, I., Abbotts, R., Beebeejaun, S., Storr, S. J., …Madhusudan, S. (2013). Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?. Antioxidants and Redox Signaling, 18(18), https://doi.org/10.1089/ars.2012.4873

Chronic inflammation is a driving force for gastric carcinogenesis. Reactive oxygen species (ROS) generated during the inflammatory process generates DNA damage that is processed through the DNA repair pathways. In this study, we profiled key DNA rep... Read More about Are DNA repair factors promising biomarkers for personalized therapy in gastric cancer?.

Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells (2013)
Journal Article
Sultana, R., Abdel-Fatah, T., Perry, C., Moseley, P., Albarakti, N., Mohan, V., …Madhusudan, S. (2013). Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells. PLoS ONE, 8(2), Article e57098. https://doi.org/10.1371/journal.pone.0057098

Introduction Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is a key sensor of single-stranded DNA associated with stalled replication forks and repair intermediates generated during DNA repair. XRCC1 is a critical enzyme in sin... Read More about Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells.

Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla (2012)
Journal Article
Storr, S. J., Zaitoun, A. M., Arora, A., Durrant, L. G., Lobo, D. N., Madhusudan, S., & Martin, S. G. (2012). Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla. BMC Cancer, 12(511), https://doi.org/10.1186/1471-2407-12-511

Background: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. Methods: We assessed the expression of calpai... Read More about Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla.

Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy (2012)
Journal Article
Fareed, K. R., Soomro, I. N., Hameed, K., Arora, A., Lobo, D. N., Parsons, S. L., & Madhusudan, S. (2012). Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy. World Journal of Gastroenterology, 18(16), https://doi.org/10.3748/wjg.v18.i16.1915

AIM: To examine cytokeratin-18 (CK-18) and caspase-cleaved CK-18 expression in tumours and correlate with clinicopathological outcomes including tumour regression grade (TRG) response. METHODS: Formalin-fixed human gastro-oesophageal cancers were... Read More about Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy.