Outputs (57)

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., Seedhouse, C., Mirza, S., Band, V., Rakha, E. 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., Walgren, R. A., & 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., Chan, S. Y., Savva, C., Schiavone, K., Carmell, N., Myers, K. N., Rakha, E. A., Madhusudan, S., & 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., Anthoney, A., Corrie, P. G., Madhusudan, S., Maraveyas, A., Ross, P. J., Waters, J. S., Steward, W. P., Rees, C., McNamara, M. G., Beare, S., Bridgewater, J. A., Dive, C., & 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.

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., Ellis, I. O., Rakha, E., & 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., Campbell, J., Mirza, H., Grigoriadis, A., Tutt, A., Moseley, P. M., Abdel-Fatah, T. M., Chan, S. Y., Madhusudan, S., Rhaka, E. A., Ellis, I. O., Lord, C. J., Yuan, Y., Green, A. R., & 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.

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., Evans, A., Shaw, V. E., Wadsley, J., Valle, J. W., Propper, D., Wasan, H., Falk, S., Cunningham, D., Coxon, F., Ross, P., Madhusudan, S., Wadd, N., Corrie, P., Hickish, 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.

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., Rakha, E., Ellis, I. O., & 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.

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., Green, A. R., Ball, G. R., Rakha, E. A., Ellis, I. O., Sharma, S., & 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.