All Outputs (77)

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.