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1. BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance

Author

Nesic, Ksenija, Krais, John J., Wang, Yifan, Vandenberg, Cassandra J., Patel, Pooja, Cai, Kathy Q., Kwan, Tanya, Lieschke, Elizabeth, Ho, Gwo-Yaw, Barker, Holly E., Bedo, Justin, Casadei, Silvia, Farrell, Andrew, Radke, Marc, Shield-Artin, Kristy, Penington, Jocelyn S., Geissler, Franziska, Kyran, Elizabeth, Betsch, Robert, Xu, Lijun, Zhang, Fan, Dobrovic, Alexander, Olesen, Inger, Kristeleit, Rebecca, Oza, Amit, McNeish, Iain, Ratnayake, Gayanie, Traficante, Nadia, DeFazio, Anna, Bowtell, David D. L., Harding, Thomas C., Lin, Kevin, Swisher, Elizabeth M., Kondrashova, Olga, Scott, Clare L., Johnson, Neil, and Wakefield, Matthew J.

Published
2024
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2. Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

Author

Meagher, Nicola S, Gorringe, Kylie L, Wakefield, Matthew, Bolithon, Adelyn, Pang, Chi Nam Ignatius, Chiu, Derek S, Anglesio, Michael S, Mallitt, Kylie-Ann, Doherty, Jennifer A, Harris, Holly R, Schildkraut, Joellen M, Berchuck, Andrew, Cushing-Haugen, Kara L, Chezar, Ksenia, Chou, Angela, Tan, Adeline, Alsop, Jennifer, Barlow, Ellen, Beckmann, Matthias W, Boros, Jessica, Bowtell, David DL, Group, for the AOCS, Brand, Alison H, Brenton, James D, Campbell, Ian, Cheasley, Dane, Cohen, Joshua, Cybulski, Cezary, Elishaev, Esther, Erber, Ramona, Farrell, Rhonda, Fischer, Anna, Fu, Zhuxuan, Gilks, Blake, Gill, Anthony J, Initiative, for the Australian Pancreatic Genome, Gourley, Charlie, Grube, Marcel, Harnett, Paul R, Hartmann, Arndt, Hettiaratchi, Anusha, Høgdall, Claus K, Huzarski, Tomasz, Jakubowska, Anna, Jimenez-Linan, Mercedes, Kennedy, Catherine J, Kim, Byoung-Gie, Kim, Jae-Weon, Kim, Jae-Hoon, Klett, Kayla, Koziak, Jennifer M, Lai, Tiffany, Laslavic, Angela, Lester, Jenny, Leung, Yee, Li, Na, Liauw, Winston, Lim, Belle WX, Linder, Anna, Lubiński, Jan, Mahale, Sakshi, Mateoiu, Constantina, McInerny, Simone, Menkiszak, Janusz, Minoo, Parham, Mittelstadt, Suzana, Morris, David, Orsulic, Sandra, Park, Sang-Yoon, Pearce, Celeste Leigh, Pearson, John V, Pike, Malcolm C, Quinn, Carmel M, Mohan, Ganendra Raj, Rao, Jianyu, Riggan, Marjorie J, Ruebner, Matthias, Salfinger, Stuart, Scott, Clare L, Shah, Mitul, Steed, Helen, Stewart, Colin JR, Subramanian, Deepak, Sung, Soseul, Tang, Katrina, Timpson, Paul, Ward, Robyn L, Wiedenhoefer, Rebekka, Thorne, Heather, Investigators, for the kConFab, Cohen, Paul A, Crowe, Philip, Fasching, Peter A, Gronwald, Jacek, Hawkins, Nicholas J, Høgdall, Estrid, Huntsman, David G, James, Paul A, Karlan, Beth Y, and Kelemen, Linda E

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Ovarian Cancer, Rare Diseases, Cancer, Digestive Diseases, Genetics, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Female, Humans, Neoplasm Staging, Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Adenocarcinoma, Mucinous, Prognosis, Gastrointestinal Neoplasms, AOCS Group, Australian Pancreatic Genome Initiative, kConFab Investigators, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeAdvanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features.Experimental designDiscovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55).ResultsInfiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04-7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04-1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01-1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%).ConclusionsAn infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies.

Published
2022

3. CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer

Author

Xu, Haineng, Gitto, Sarah B., Ho, Gwo-Yaw, Medvedev, Sergey, Shield-Artin, Kristy, Kim, Hyoung, Beard, Sally, Kinose, Yasuto, Wang, Xiaolei, Barker, Holly E., Ratnayake, Gayanie, Hwang, Wei-Ting, Hansen, Ryan J., Strouse, Bryan, Milutinovic, Snezana, Hassig, Christian, Wakefield, Matthew J., Vandenberg, Cassandra J., Scott, Clare L., and Simpkins, Fiona

Published
2024
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4. Interferon-ε is a tumour suppressor and restricts ovarian cancer

Author

Marks, Zoe R. C., Campbell, Nicole K., Mangan, Niamh E., Vandenberg, Cassandra J., Gearing, Linden J., Matthews, Antony Y., Gould, Jodee A., Tate, Michelle D., Wray-McCann, Georgie, Ying, Le, Rosli, Sarah, Brockwell, Natasha, Parker, Belinda S., Lim, San S., Bilandzic, Maree, Christie, Elizabeth L., Stephens, Andrew N., de Geus, Eveline, Wakefield, Matthew J., Ho, Gwo-Yaw, McNally, Orla, McNeish, Iain A., Bowtell, David D. L., de Weerd, Nicole A., Scott, Clare L., Bourke, Nollaig M., and Hertzog, Paul J.

Published
2023
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5. Targeting homologous recombination deficiency in uterine leiomyosarcoma

Author

Dall, Genevieve, Vandenberg, Cassandra J., Nesic, Ksenija, Ratnayake, Gayanie, Zhu, Wenying, Vissers, Joseph H. A., Bedő, Justin, Penington, Jocelyn, Wakefield, Matthew J., Kee, Damien, Carmagnac, Amandine, Lim, Ratana, Shield-Artin, Kristy, Milesi, Briony, Lobley, Amanda, Kyran, Elizabeth L., O’Grady, Emily, Tram, Joshua, Zhou, Warren, Nugawela, Devindee, Stewart, Kym Pham, Caldwell, Reece, Papadopoulos, Lia, Ng, Ashley P., Dobrovic, Alexander, Fox, Stephen B., McNally, Orla, Power, Jeremy D., Meniawy, Tarek, Tan, Teng Han, Collins, Ian M., Klein, Oliver, Barnett, Stephen, Olesen, Inger, Hamilton, Anne, Hofmann, Oliver, Grimmond, Sean, Papenfuss, Anthony T., Scott, Clare L., and Barker, Holly E.

Published
2023
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6. A risk-reward examination of sample multiplexing reagents for single cell RNA-Seq

Author

Brown, Daniel V., Anttila, Casey J.A., Ling, Ling, Grave, Patrick, Baldwin, Tracey M., Munnings, Ryan, Farchione, Anthony J., Bryant, Vanessa L., Dunstone, Amelia, Biben, Christine, Taoudi, Samir, Weber, Tom S., Naik, Shalin H., Hadla, Anthony, Barker, Holly E., Vandenberg, Cassandra J., Dall, Genevieve, Scott, Clare L., Moore, Zachery, Whittle, James R., Freytag, Saskia, Best, Sarah A., Papenfuss, Anthony T., Olechnowicz, Sam W.Z., MacRaild, Sarah E., Wilcox, Stephen, Hickey, Peter F., Amann-Zalcenstein, Daniela, and Bowden, Rory

Published
2024
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7. Multiomic analysis of homologous recombination-deficient end-stage high-grade serous ovarian cancer

Author

Burdett, Nikki L., Willis, Madelynne O., Alsop, Kathryn, Hunt, Allison L., Pandey, Ahwan, Hamilton, Phineas T., Abulez, Tamara, Liu, Xuan, Hoang, Therese, Craig, Stuart, Fereday, Sian, Hendley, Joy, Garsed, Dale W., Milne, Katy, Kalaria, Shreena, Marshall, Ashley, Hood, Brian L., Wilson, Katlin N., Conrads, Kelly A., Pishas, Kathleen I., Ananda, Sumitra, Scott, Clare L., Antill, Yoland, McNally, Orla, Mileshkin, Linda, Hamilton, Anne, Au-Yeung, George, Devereux, Lisa, Thorne, Heather, Bild, Andrea, Bateman, Nicholas W., Maxwell, G. Larry, Chang, Jeffrey T., Conrads, Thomas P., Nelson, Brad H., Bowtell, David D. L., and Christie, Elizabeth L.

Published
2023
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8. Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer

Author

Hoppe, Michal M, Jaynes, Patrick, Wardyn, Joanna D, Upadhyayula, Sai Srinivas, Tan, Tuan Zea, Lie, Stefanus, Lim, Diana GZ, Pang, Brendan NK, Lim, Sherlly, Yeong, Joe PS, Karnezis, Anthony, Chiu, Derek S, Leung, Samuel, Huntsman, David G, Sedukhina, Anna S, Sato, Ko, Topp, Monique D, Scott, Clare L, Choi, Hyungwon, Patel, Naina R, Brown, Robert, Kaye, Stan B, Pitt, Jason J, Tan, David SP, and Jeyasekharan, Anand D

Subjects
Rare Diseases, Cancer, Genetics, Ovarian Cancer, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Carcinoma, Ovarian Epithelial, Female, Humans, Neoplasm Recurrence, Local, Ovarian Neoplasms, Paclitaxel, Platinum, Rad51 Recombinase, HRD, immune exclusion, multiplexed IHC, ovarian cancer, RAD51, Biological Sciences, Medical and Health Sciences
Abstract

Early relapse after platinum chemotherapy in epithelial ovarian cancer (EOC) portends poor survival. A-priori identification of platinum resistance is therefore crucial to improve on standard first-line carboplatin-paclitaxel treatment. The DNA repair pathway homologous recombination (HR) repairs platinum-induced damage, and the HR recombinase RAD51 is overexpressed in cancer. We therefore designed a REMARK-compliant study of pre-treatment RAD51 expression in EOC, using fluorescent quantitative immunohistochemistry (qIHC) to overcome challenges in quantitation of protein expression in situ. In a discovery cohort (n = 284), RAD51-High tumours had shorter progression-free and overall survival compared to RAD51-Low cases in univariate and multivariate analyses. The association of RAD51 with relapse/survival was validated in a carboplatin monotherapy SCOTROC4 clinical trial cohort (n = 264) and was predominantly noted in HR-proficient cancers (Myriad HRDscore

Published
2021

9. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2).

Author

Swisher, Elizabeth M, Kwan, Tanya T, Oza, Amit M, Tinker, Anna V, Ray-Coquard, Isabelle, Oaknin, Ana, Coleman, Robert L, Aghajanian, Carol, Konecny, Gottfried E, O'Malley, David M, Leary, Alexandra, Provencher, Diane, Welch, Stephen, Chen, Lee-May, Wahner Hendrickson, Andrea E, Ma, Ling, Ghatage, Prafull, Kristeleit, Rebecca S, Dorigo, Oliver, Musafer, Ashan, Kaufmann, Scott H, Elvin, Julia A, Lin, Douglas I, Chambers, Setsuko K, Dominy, Erin, Vo, Lan-Thanh, Goble, Sandra, Maloney, Lara, Giordano, Heidi, Harding, Thomas, Dobrovic, Alexander, Scott, Clare L, Lin, Kevin K, and McNeish, Iain A

Subjects
Humans, Ovarian Neoplasms, Neoplasm Recurrence, Local, Platinum, Indoles, DNA-Binding Proteins, BRCA1 Protein, BRCA2 Protein, Antineoplastic Agents, DNA Methylation, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Promoter Regions, Genetic, Poly(ADP-ribose) Polymerase Inhibitors, Carcinoma, Ovarian Epithelial
Abstract

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity.

Published
2021

11. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Coleman, Robert L, Oza, Amit M, Lorusso, Domenica, Aghajanian, Carol, Oaknin, Ana, Dean, Andrew, Colombo, Nicoletta, Weberpals, Johanne I, Clamp, Andrew, Scambia, Giovanni, Leary, Alexandra, Holloway, Robert W, Gancedo, Margarita Amenedo, Fong, Peter C, Goh, Jeffrey C, O'Malley, David M, Armstrong, Deborah K, Garcia-Donas, Jesus, Swisher, Elizabeth M, Floquet, Anne, Konecny, Gottfried E, McNeish, Iain A, Scott, Clare L, Cameron, Terri, Maloney, Lara, Isaacson, Jeff, Goble, Sandra, Grace, Caroline, Harding, Thomas C, Raponi, Mitch, Sun, James, Lin, Kevin K, Giordano, Heidi, Ledermann, Jonathan A, investigators, ARIEL3, Buck, M, Dean, A, Friedlander, ML, Goh, JC, Harnett, P, Kichenadasse, G, Scott, CL, Denys, H, Dirix, L, Vergote, I, Elit, L, Ghatage, P, Oza, AM, Plante, M, Provencher, D, Weberpals, JI, Welch, S, Floquet, A, Gladieff, L, Joly, F, Leary, A, Lortholary, A, Lotz, J, Medioni, J, Tredan, O, You, B, El-Balat, A, Hänle, C, Krabisch, P, Neunhöffer, T, Pölcher, M, Wimberger, P, Amit, A, Kovel, S, Leviov, M, Safra, T, Shapira-Frommer, R, Stemmer, S, Bologna, A, Colombo, N, Lorusso, D, Pignata, S, Sabbatini, RF, Scambia, G, Tamberi, S, Zamagni, C, Fong, PC, O'Donnell, A, Gancedo, M Amenedo, Herraez, A Casado, Garcia-Donas, J, Guerra, EM, Oaknin, A, Palacio, I, Romero, I, Sanchez, A, Banerjee, SN, Clamp, A, Drew, Y, Gabra, HG, Jackson, D, Ledermann, JA, McNeish, IA, Parkinson, C, and Powell, M

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Clinical Research, Cancer, Genetics, Clinical Trials and Supportive Activities, Ovarian Cancer, Rare Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, 6.2 Cellular and gene therapies, Aged, Disease-Free Survival, Double-Blind Method, Female, Follow-Up Studies, Humans, Indoles, Internationality, Maintenance Chemotherapy, Middle Aged, Molecular Targeted Therapy, Neoplasm Recurrence, Local, Ovarian Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Risk Assessment, Survival Rate, Treatment Outcome, ARIEL3 investigators, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundRucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.FindingsBetween April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16-0·34]; p

Published
2017

12. Prognostic nomogram for progression-free survival in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer on maintenance olaparib therapy following response to chemotherapy

Author

Tjokrowidjaja, Angelina, Friedlander, Michael, Lord, Sarah J., Asher, Rebecca, Rodrigues, Manuel, Ledermann, Jonathan A., Matulonis, Ursula A., Oza, Amit M., Bruchim, Ilan, Huzarski, Tomasz, Gourley, Charlie, Harter, Philipp, Vergote, Ignace, Scott, Clare L., Meier, Werner, Shapira-Frommer, Ronnie, Milenkova, Tsveta, Pujade-Lauraine, Eric, Gebski, Val, and Lee, Chee K.

Published
2021
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13. Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses

Author

Kang, Eun Young, Cheasley, Dane, LePage, Cecile, Wakefield, Matthew J., da Cunha Torres, Michelle, Rowley, Simone, Salazar, Carolina, Xing, Zhongyue, Allan, Prue, Bowtell, David D.L., Mes-Masson, Anne-Marie, Provencher, Diane M., Rahimi, Kurosh, Kelemen, Linda E., Fasching, Peter A., Doherty, Jennifer A., Goodman, Marc T., Goode, Ellen L., Deen, Suha, Pharoah, Paul D.P., Brenton, James D., Sieh, Weiva, Mateoiu, Constantina, Sundfeldt, Karin, Cook, Linda S., Le, Nhu D., Anglesio, Michael S., Gilks, C. Blake, Huntsman, David G., Kennedy, Catherine J., Traficante, Nadia, Bowtell, D., Chenevix-Trench, G., Green, A., Webb, P., DeFazio, A., Gertig, D., Traficante, N., Fereday, S., Moore, S., Hung, J., Harrap, K., Sadkowsky, T., Pandeya, N., Malt, M., Mellon, A., Robertson, R., Bergh, T. Vanden, Jones, M., Mackenzie, P., Maidens, J., Nattress, K., Chiew, Y.E., Stenlake, A., Sullivan, H., Alexander, B., Ashover, P., Brown, S., Corrish, T., Green, L., Jackman, L., Ferguson, K., Martin, K., Martyn, A., Ranieri, B., White, J., Jayde, V., Mamers, P., Bowes, L., Galletta, L., Giles, D., Hendley, J., Alsop, K., Schmidt, T., Shirley, H., Ball, C., Young, C., Viduka, S., Tran, Hoa, Bilic, Sanela, Glavinas, Lydia, Brooks, Julia, Stuart-Harris, R., Kirsten, F., Rutovitz, J., Clingan, P., Glasgow, A., Proietto, A., Braye, S., Otton, G., Shannon, J., Bonaventura, T., Stewart, J., Begbie, S., Friedlander, M., Bell, D., Baron-Hay, S., Ferrier, A., Gard, G., Nevell, D., Pavlakis, N., Valmadre, S., Young, B., Camaris, C., Crouch, R., Edwards, L., Hacker, N., Marsden, D., Robertson, G., Beale, P., Beith, J., Carter, J., Dalrymple, C., Houghton, R., Russell, P., Links, M., Grygiel, J., Hill, J., Brand, A., Byth, K., Jaworski, R., Harnett, P., Sharma, R., Wain, G., Ward, B., Papadimos, D., Crandon, A., Cummings, M., Horwood, K., Obermair, A., Perrin, L., Wyld, D., Nicklin, J., Davy, M., Oehler, M.K., Hall, C., Dodd, T., Healy, T., Pittman, K., Henderson, D., Miller, J., Pierdes, J., Blomfield, P., Challis, D., McIntosh, R., Parker, A., Brown, B., Rome, R., Allen, D., Grant, P., Hyde, S., Laurie, R., Robbie, M., Healy, D., Jobling, T., Manolitsas, T., McNealage, J., Rogers, P., Susil, B., Sumithran, E., Simpson, I., Phillips, K., Rischin, D., Fox, S., Johnson, D., Lade, S., Loughrey, M., O'Callaghan, N., Murray, W., Waring, P., Billson, V., Pyman, J., Neesham, D., Quinn, M., Underhill, C., Bell, R., Ng, L.F., Blum, R., Ganju, V., Hammond, I., Leung, Y., McCartney, A., Buck, M., Haviv, I., Purdie, D., Whiteman, D., Zeps, N., DeFazio, Anna, Kaufmann, Scott, Churchman, Michael, Gourley, Charlie, Stephens, Andrew N., Meagher, Nicola S., Ramus, Susan J., Antill, Yoland C., Campbell, Ian, Scott, Clare L., Köbel, Martin, Gorringe, Kylie L., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Ananda, Sumitra, Au-Yeung, George, Böhm, Maret, Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Dudley, Rhiannon, Fairweather, Nicole, Fereday, Sian, Fox, Stephen B., Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Le Page, Cecile, McNally, Orla M., McAlpine, Jessica N., Mileshkin, Linda, Pyman, Jan, Samimi, Goli, Sharma, Ragwha, and Campbell, Ian G.

Published
2021
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14. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial

Author

Swisher, Elizabeth M, Lin, Kevin K, Oza, Amit M, Scott, Clare L, Giordano, Heidi, Sun, James, Konecny, Gottfried E, Coleman, Robert L, Tinker, Anna V, O'Malley, David M, Kristeleit, Rebecca S, Ma, Ling, Bell-McGuinn, Katherine M, Brenton, James D, Cragun, Janiel M, Oaknin, Ana, Ray-Coquard, Isabelle, Harrell, Maria I, Mann, Elaina, Kaufmann, Scott H, Floquet, Anne, Leary, Alexandra, Harding, Thomas C, Goble, Sandra, Maloney, Lara, Isaacson, Jeff, Allen, Andrew R, Rolfe, Lindsey, Yelensky, Roman, Raponi, Mitch, and McNeish, Iain A

Subjects
Rare Diseases, Genetics, Cancer, Ovarian Cancer, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Aged, Antineoplastic Agents, BRCA1 Protein, BRCA2 Protein, Carcinoma, Ovarian Epithelial, Drug Resistance, Neoplasm, Fallopian Tube Neoplasms, Female, Follow-Up Studies, Germ-Line Mutation, Humans, Indoles, International Agencies, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms, Platinum, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases, Prognosis, Prospective Studies, Salvage Therapy, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundPoly(ADP-ribose) polymerase (PARP) inhibitors have activity in ovarian carcinomas with homologous recombination deficiency. Along with BRCA1 and BRCA2 (BRCA) mutations genomic loss of heterozygosity (LOH) might also represent homologous recombination deficiency. In ARIEL2, we assessed the ability of tumour genomic LOH, quantified with a next-generation sequencing assay, to predict response to rucaparib, an oral PARP inhibitor.MethodsARIEL2 is an international, multicentre, two-part, phase 2, open-label study done at 49 hospitals and cancer centres in Australia, Canada, France, Spain, the UK, and the USA. In ARIEL2 Part 1, patients with recurrent, platinum-sensitive, high-grade ovarian carcinoma were classified into one of three predefined homologous recombination deficiency subgroups on the basis of tumour mutational analysis: BRCA mutant (deleterious germline or somatic), BRCA wild-type and LOH high (LOH high group), or BRCA wild-type and LOH low (LOH low group). We prespecified a cutoff of 14% or more genomic LOH for LOH high. Patients began treatment with oral rucaparib at 600 mg twice per day for continuous 28 day cycles until disease progression or any other reason for discontinuation. The primary endpoint was progression-free survival. All patients treated with at least one dose of rucaparib were included in the safety analyses and all treated patients who were classified were included in the primary endpoint analysis. This trial is registered with ClinicalTrials.gov, number NCT01891344. Enrolment into ARIEL2 Part 1 is complete, although an extension (Part 2) is ongoing.Findings256 patients were screened and 206 were enrolled between Oct 30, 2013, and Dec 19, 2014. At the data cutoff date (Jan 18, 2016), 204 patients had received rucaparib, with 28 patients remaining in the study. 192 patients could be classified into one of the three predefined homologous recombination deficiency subgroups: BRCA mutant (n=40), LOH high (n=82), or LOH low (n=70). Tumours from 12 patients were established as BRCA wild-type, but could not be classified for LOH, because of insufficient neoplastic nuclei in the sample. The median duration of treatment for the 204 patients was 5·7 months (IQR 2·8-10·1). 24 patients in the BRCA mutant subgroup, 56 patients in the LOH high subgroup, and 59 patients in the LOH low subgroup had disease progression or died. Median progression-free survival after rucaparib treatment was 12·8 months (95% CI 9·0-14·7) in the BRCA mutant subgroup, 5·7 months (5·3-7·6) in the LOH high subgroup, and 5·2 months (3·6-5·5) in the LOH low subgroup. Progression-free survival was significantly longer in the BRCA mutant (hazard ratio 0·27, 95% CI 0·16-0·44, p

Published
2017

16. RAF1 rearrangements are common in pancreatic acinar cell carcinomas

Author

Prall, Owen W.J., Nastevski, Violeta, Xu, Huiling, McEvoy, Christopher R.E., Vissers, Joep H.A., Byrne, David J., Takano, Elena, Yerneni, Satwica, Ellis, Sarah, Green, Thomas, Mitchell, Catherine A., Murray, William K., Scott, Clare L., Grimmond, Sean M., Hofmann, Oliver, Papenfuss, Anthony, Kee, Damien, Fellowes, Andrew, Brown, Ian S., Miller, Gregory, Kumarasinghe, M. Priyanthi, Perren, Aurel, Nahm, Christopher B., Mittal, Anubhav, Samra, Jaswinder, Ahadi, Mahsa, Fox, Stephen B., Chou, Angela, and Gill, Anthony J.

Published
2020
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17. Therapeutic options for mucinous ovarian carcinoma

Author

Gorringe, Kylie L., Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Amarasinghe, Kaushalya C., Ananda, Sumitra, Bowtell, David D.L., Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Fereday, Sian, Gilks, C. Blake, Gourley, Charlie, Hadley, Alison M., Hendley, Joy, Hunter, Sally M., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, Li, Jason, Lupat, Richard, McNally, Orla M., McAlpine, Jessica N., Pyman, Jan, Rowley, Simone M., Salazar, Carolina, Saunders, Hugo, Semple, Timothy, Stephens, Andrew N., Thio, Niko, Torres, Michelle C., Traficante, Nadia, Zethoven, Magnus, Antill, Yoland C., Campbell, Ian G., and Scott, Clare L.

Published
2020
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18. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

Author

Bowtell, David D, Böhm, Steffen, Ahmed, Ahmed A, Aspuria, Paul-Joseph, Bast, Robert C, Beral, Valerie, Berek, Jonathan S, Birrer, Michael J, Blagden, Sarah, Bookman, Michael A, Brenton, James D, Chiappinelli, Katherine B, Martins, Filipe Correia, Coukos, George, Drapkin, Ronny, Edmondson, Richard, Fotopoulou, Christina, Gabra, Hani, Galon, Jérôme, Gourley, Charlie, Heong, Valerie, Huntsman, David G, Iwanicki, Marcin, Karlan, Beth Y, Kaye, Allyson, Lengyel, Ernst, Levine, Douglas A, Lu, Karen H, McNeish, Iain A, Menon, Usha, Narod, Steven A, Nelson, Brad H, Nephew, Kenneth P, Pharoah, Paul, Powell, Daniel J, Ramos, Pilar, Romero, Iris L, Scott, Clare L, Sood, Anil K, Stronach, Euan A, and Balkwill, Frances R

Subjects
Cancer, Ovarian Cancer, Prevention, Rare Diseases, Good Health and Well Being, Cystadenocarcinoma, Serous, Female, Humans, Neoplasm Grading, Ovarian Neoplasms, Prognosis, Survival Rate, Medical and Health Sciences, Oncology & Carcinogenesis
Abstract

High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.

Published
2015

20. Supplementary Data from Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin

Author

Ho, Gwo Yaw, primary, Kyran, Elizabeth L., primary, Bedo, Justin, primary, Wakefield, Matthew J., primary, Ennis, Darren P., primary, Mirza, Hasan B., primary, Vandenberg, Cassandra J., primary, Lieschke, Elizabeth, primary, Farrell, Andrew, primary, Hadla, Anthony, primary, Lim, Ratana, primary, Dall, Genevieve, primary, Vince, James E., primary, Chua, Ngee Kiat, primary, Kondrashova, Olga, primary, Upstill-Goddard, Rosanna, primary, Bailey, Ulla-Maja, primary, Dowson, Suzanne, primary, Roxburgh, Patricia, primary, Glasspool, Rosalind M., primary, Bryson, Gareth, primary, Biankin, Andrew V., primary, Cooke, Susanna L., primary, Ratnayake, Gayanie, primary, McNally, Orla, primary, Traficante, Nadia, primary, DeFazio, Anna, primary, Weroha, S. John, primary, Bowtell, David D., primary, McNeish, Iain A., primary, Papenfuss, Anthony T., primary, Scott, Clare L., primary, and Barker, Holly E., primary

Published
2023
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21. Data from Epithelial-to-Mesenchymal Transition Supports Ovarian Carcinosarcoma Tumorigenesis and Confers Sensitivity to Microtubule Targeting with Eribulin

Author

Ho, Gwo Yaw, primary, Kyran, Elizabeth L., primary, Bedo, Justin, primary, Wakefield, Matthew J., primary, Ennis, Darren P., primary, Mirza, Hasan B., primary, Vandenberg, Cassandra J., primary, Lieschke, Elizabeth, primary, Farrell, Andrew, primary, Hadla, Anthony, primary, Lim, Ratana, primary, Dall, Genevieve, primary, Vince, James E., primary, Chua, Ngee Kiat, primary, Kondrashova, Olga, primary, Upstill-Goddard, Rosanna, primary, Bailey, Ulla-Maja, primary, Dowson, Suzanne, primary, Roxburgh, Patricia, primary, Glasspool, Rosalind M., primary, Bryson, Gareth, primary, Biankin, Andrew V., primary, Cooke, Susanna L., primary, Ratnayake, Gayanie, primary, McNally, Orla, primary, Traficante, Nadia, primary, DeFazio, Anna, primary, Weroha, S. John, primary, Bowtell, David D., primary, McNeish, Iain A., primary, Papenfuss, Anthony T., primary, Scott, Clare L., primary, and Barker, Holly E., primary

Published
2023
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22. A Matched Molecular and Clinical Analysis of the Epithelioid Haemangioendothelioma Cohort in the Stafford Fox Rare Cancer Program and Contextual Literature Review

Author

Abdelmogod, Arwa, primary, Papadopoulos, Lia, additional, Riordan, Stephen, additional, Wong, Melvin, additional, Weltman, Martin, additional, Lim, Ratana, additional, McEvoy, Christopher, additional, Fellowes, Andrew, additional, Fox, Stephen, additional, Bedő, Justin, additional, Penington, Jocelyn, additional, Pham, Kym, additional, Hofmann, Oliver, additional, Vissers, Joseph H. A., additional, Grimmond, Sean, additional, Ratnayake, Gayanie, additional, Christie, Michael, additional, Mitchell, Catherine, additional, Murray, William K., additional, McClymont, Kelly, additional, Luk, Peter, additional, Papenfuss, Anthony T., additional, Kee, Damien, additional, Scott, Clare L., additional, Goldstein, David, additional, and Barker, Holly E., additional

Published
2023
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23. Preclinical small molecule WEHI-7326 overcomes drug resistance and elicits response in patient-derived xenograft models of human treatment-refractory tumors

Author

Grohmann, Christoph, Walker, Francesca, Devlin, Mark, Luo, Meng-Xiao, Chüeh, Anderly C., Doherty, Judy, Vaillant, François, Ho, Gwo-Yaw, Wakefield, Matthew J., Weeden, Clare E., Kamili, Alvin, Murray, Jayne, Po’uha, Sela T., Weinstock, Janet, Kane, Serena R., Faux, Maree C., Broekhuizen, Esmee, Zheng, Ye, Shield-Artin, Kristy, Kershaw, Nadia J., Tan, Chin Wee, Witchard, Helen M., Ebert, Gregor, Charman, Susan A., Street, Ian, Kavallaris, Maria, Haber, Michelle, Fletcher, Jamie I., Asselin-Labat, Marie-Liesse, Scott, Clare L., Visvader, Jane E., Lindeman, Geoffrey J., Watson, Keith G., Burgess, Antony W., and Lessene, Guillaume

Published
2021
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24. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Buck, M, Dean, A, Friedlander, M L, Goh, J C, Harnett, P, Kichenadasse, G, Scott, C L, Denys, H, Dirix, L, Vergote, I, Elit, L, Ghatage, P, Oza, A M, Plante, M, Provencher, D, Weberpals, J I, Welch, S, Floquet, A, Gladieff, L, Joly, F, Leary, A, Lortholary, A, Lotz, J, Medioni, J, Tredan, O, You, B, El-Balat, A, Hänle, C, Krabisch, P, Neunhöffer, T, Pölcher, M, Wimberger, P, Amit, A, Kovel, S, Leviov, M, Safra, T, Shapira-Frommer, R, Stemmer, S, Bologna, A, Colombo, N, Lorusso, D, Pignata, S, Sabbatini, R F, Scambia, G, Tamberi, S, Zamagni, C, Fong, P C, O'Donnell, A, Gancedo, M Amenedo, Herraez, A Casado, Garcia-Donas, J, Guerra, E M, Oaknin, A, Palacio, I, Romero, I, Sanchez, A, Banerjee, S N, Clamp, A, Drew, Y, Gabra, H G, Jackson, D, Ledermann, J A, McNeish, I A, Parkinson, C, Powell, M, Aghajanian, C, Armstrong, D K, Birrer, M J, Buss, M K, Chambers, S K, Chen, L-m, Coleman, R L, Holloway, R W, Konecny, G E, Ma, L, Morgan, M A, Morris, R T, Mutch, D G, O'Malley, D M, Slomovitz, B M, Swisher, E M, Vanderkwaak, T, Vulfovich, M, Coleman, Robert L, Oza, Amit M, Lorusso, Domenica, Aghajanian, Carol, Oaknin, Ana, Dean, Andrew, Colombo, Nicoletta, Weberpals, Johanne I, Clamp, Andrew, Scambia, Giovanni, Leary, Alexandra, Holloway, Robert W, Gancedo, Margarita Amenedo, Fong, Peter C, Goh, Jeffrey C, O'Malley, David M, Armstrong, Deborah K, Garcia-Donas, Jesus, Swisher, Elizabeth M, Floquet, Anne, Konecny, Gottfried E, McNeish, Iain A, Scott, Clare L, Cameron, Terri, Maloney, Lara, Isaacson, Jeff, Goble, Sandra, Grace, Caroline, Harding, Thomas C, Raponi, Mitch, Sun, James, Lin, Kevin K, Giordano, Heidi, and Ledermann, Jonathan A

Published
2017
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26. Data from Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Kondrashova, Olga, primary, Nguyen, Minh, primary, Shield-Artin, Kristy, primary, Tinker, Anna V., primary, Teng, Nelson N.H., primary, Harrell, Maria I., primary, Kuiper, Michael J., primary, Ho, Gwo-Yaw, primary, Barker, Holly, primary, Jasin, Maria, primary, Prakash, Rohit, primary, Kass, Elizabeth M., primary, Sullivan, Meghan R., primary, Brunette, Gregory J., primary, Bernstein, Kara A., primary, Coleman, Robert L., primary, Floquet, Anne, primary, Friedlander, Michael, primary, Kichenadasse, Ganessan, primary, O'Malley, David M., primary, Oza, Amit, primary, Sun, James, primary, Robillard, Liliane, primary, Maloney, Lara, primary, Bowtell, David, primary, Giordano, Heidi, primary, Wakefield, Matthew J., primary, Kaufmann, Scott H., primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Raponi, Mitch, primary, McNeish, Iain A., primary, Swisher, Elizabeth M., primary, Lin, Kevin K., primary, and Scott, Clare L., primary

Published
2023
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27. Table S2 from BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Lin, Kevin K., primary, Harrell, Maria I., primary, Oza, Amit M., primary, Oaknin, Ana, primary, Ray-Coquard, Isabelle, primary, Tinker, Anna V., primary, Helman, Elena, primary, Radke, Marc R., primary, Say, Carmen, primary, Vo, Lan-Thanh, primary, Mann, Elaina, primary, Isaacson, Jeffrey D., primary, Maloney, Lara, primary, O'Malley, David M., primary, Chambers, Setsuko K., primary, Kaufmann, Scott H., primary, Scott, Clare L., primary, Konecny, Gottfried E., primary, Coleman, Robert L., primary, Sun, James X., primary, Giordano, Heidi, primary, Brenton, James D., primary, Harding, Thomas C., primary, McNeish, Iain A., primary, and Swisher, Elizabeth M., primary

Published
2023
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28. Supplementary Tables and Supplementary Figures 1 through 11 from Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Kondrashova, Olga, primary, Nguyen, Minh, primary, Shield-Artin, Kristy, primary, Tinker, Anna V., primary, Teng, Nelson N.H., primary, Harrell, Maria I., primary, Kuiper, Michael J., primary, Ho, Gwo-Yaw, primary, Barker, Holly, primary, Jasin, Maria, primary, Prakash, Rohit, primary, Kass, Elizabeth M., primary, Sullivan, Meghan R., primary, Brunette, Gregory J., primary, Bernstein, Kara A., primary, Coleman, Robert L., primary, Floquet, Anne, primary, Friedlander, Michael, primary, Kichenadasse, Ganessan, primary, O'Malley, David M., primary, Oza, Amit, primary, Sun, James, primary, Robillard, Liliane, primary, Maloney, Lara, primary, Bowtell, David, primary, Giordano, Heidi, primary, Wakefield, Matthew J., primary, Kaufmann, Scott H., primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Raponi, Mitch, primary, McNeish, Iain A., primary, Swisher, Elizabeth M., primary, Lin, Kevin K., primary, and Scott, Clare L., primary

Published
2023
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30. Supp Table 1 from Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Kondrashova, Olga, primary, Nguyen, Minh, primary, Shield-Artin, Kristy, primary, Tinker, Anna V., primary, Teng, Nelson N.H., primary, Harrell, Maria I., primary, Kuiper, Michael J., primary, Ho, Gwo-Yaw, primary, Barker, Holly, primary, Jasin, Maria, primary, Prakash, Rohit, primary, Kass, Elizabeth M., primary, Sullivan, Meghan R., primary, Brunette, Gregory J., primary, Bernstein, Kara A., primary, Coleman, Robert L., primary, Floquet, Anne, primary, Friedlander, Michael, primary, Kichenadasse, Ganessan, primary, O'Malley, David M., primary, Oza, Amit, primary, Sun, James, primary, Robillard, Liliane, primary, Maloney, Lara, primary, Bowtell, David, primary, Giordano, Heidi, primary, Wakefield, Matthew J., primary, Kaufmann, Scott H., primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Raponi, Mitch, primary, McNeish, Iain A., primary, Swisher, Elizabeth M., primary, Lin, Kevin K., primary, and Scott, Clare L., primary

Published
2023
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31. Supp Table 4 from Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Kondrashova, Olga, primary, Nguyen, Minh, primary, Shield-Artin, Kristy, primary, Tinker, Anna V., primary, Teng, Nelson N.H., primary, Harrell, Maria I., primary, Kuiper, Michael J., primary, Ho, Gwo-Yaw, primary, Barker, Holly, primary, Jasin, Maria, primary, Prakash, Rohit, primary, Kass, Elizabeth M., primary, Sullivan, Meghan R., primary, Brunette, Gregory J., primary, Bernstein, Kara A., primary, Coleman, Robert L., primary, Floquet, Anne, primary, Friedlander, Michael, primary, Kichenadasse, Ganessan, primary, O'Malley, David M., primary, Oza, Amit, primary, Sun, James, primary, Robillard, Liliane, primary, Maloney, Lara, primary, Bowtell, David, primary, Giordano, Heidi, primary, Wakefield, Matthew J., primary, Kaufmann, Scott H., primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Raponi, Mitch, primary, McNeish, Iain A., primary, Swisher, Elizabeth M., primary, Lin, Kevin K., primary, and Scott, Clare L., primary

Published
2023
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33. Figures S1-S8 from BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Lin, Kevin K., primary, Harrell, Maria I., primary, Oza, Amit M., primary, Oaknin, Ana, primary, Ray-Coquard, Isabelle, primary, Tinker, Anna V., primary, Helman, Elena, primary, Radke, Marc R., primary, Say, Carmen, primary, Vo, Lan-Thanh, primary, Mann, Elaina, primary, Isaacson, Jeffrey D., primary, Maloney, Lara, primary, O'Malley, David M., primary, Chambers, Setsuko K., primary, Kaufmann, Scott H., primary, Scott, Clare L., primary, Konecny, Gottfried E., primary, Coleman, Robert L., primary, Sun, James X., primary, Giordano, Heidi, primary, Brenton, James D., primary, Harding, Thomas C., primary, McNeish, Iain A., primary, and Swisher, Elizabeth M., primary

Published
2023
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34. Supp Video from Secondary Somatic Mutations Restoring RAD51C and RAD51D Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma

Author

Kondrashova, Olga, primary, Nguyen, Minh, primary, Shield-Artin, Kristy, primary, Tinker, Anna V., primary, Teng, Nelson N.H., primary, Harrell, Maria I., primary, Kuiper, Michael J., primary, Ho, Gwo-Yaw, primary, Barker, Holly, primary, Jasin, Maria, primary, Prakash, Rohit, primary, Kass, Elizabeth M., primary, Sullivan, Meghan R., primary, Brunette, Gregory J., primary, Bernstein, Kara A., primary, Coleman, Robert L., primary, Floquet, Anne, primary, Friedlander, Michael, primary, Kichenadasse, Ganessan, primary, O'Malley, David M., primary, Oza, Amit, primary, Sun, James, primary, Robillard, Liliane, primary, Maloney, Lara, primary, Bowtell, David, primary, Giordano, Heidi, primary, Wakefield, Matthew J., primary, Kaufmann, Scott H., primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Raponi, Mitch, primary, McNeish, Iain A., primary, Swisher, Elizabeth M., primary, Lin, Kevin K., primary, and Scott, Clare L., primary

Published
2023
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37. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer

Author

Sanij, Elaine, Hannan, Katherine M., Xuan, Jiachen, Yan, Shunfei, Ahern, Jessica E., Trigos, Anna S., Brajanovski, Natalie, Son, Jinbae, Chan, Keefe T., Kondrashova, Olga, Lieschke, Elizabeth, Wakefield, Matthew J., Frank, Daniel, Ellis, Sarah, Cullinane, Carleen, Kang, Jian, Poortinga, Gretchen, Nag, Purba, Deans, Andrew J., Khanna, Kum Kum, Mileshkin, Linda, McArthur, Grant A., Soong, John, Berns, Els M. J. J., Hannan, Ross D., Scott, Clare L., Sheppard, Karen E., and Pearson, Richard B.

Published
2020
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38. Supplementary Tables from Acquired RAD51C Promoter Methylation Loss Causes PARP Inhibitor Resistance in High-Grade Serous Ovarian Carcinoma

Author

Nesic, Ksenija, primary, Kondrashova, Olga, primary, Hurley, Rachel M., primary, McGehee, Cordelia D., primary, Vandenberg, Cassandra J., primary, Ho, Gwo-Yaw, primary, Lieschke, Elizabeth, primary, Dall, Genevieve, primary, Bound, Nirashaa, primary, Shield-Artin, Kristy, primary, Radke, Marc, primary, Musafer, Ashan, primary, Chai, Zi Qing, primary, Ghamsari, Mohammad Reza Eftekhariyan, primary, Harrell, Maria I., primary, Kee, Damien, primary, Olesen, Inger, primary, McNally, Orla, primary, Traficante, Nadia, primary, Study, Australian Ovarian Cancer, primary, DeFazio, Anna, primary, Bowtell, David D.L., primary, Swisher, Elizabeth M., primary, Weroha, S. John, primary, Nones, Katia, primary, Waddell, Nicola, primary, Kaufmann, Scott H., primary, Dobrovic, Alexander, primary, Wakefield, Matthew J., primary, and Scott, Clare L., primary

Published
2023
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41. Data from Deciphering the Molecular Events Necessary for Synergistic Tumor Cell Apoptosis Mediated by the Histone Deacetylase Inhibitor Vorinostat and the BH3 Mimetic ABT-737

Author

Wiegmans, Adrian P., primary, Alsop, Amber E., primary, Bots, Michael, primary, Cluse, Leonie A., primary, Williams, Steven P., primary, Banks, Kellie-Marie, primary, Ralli, Rachael, primary, Scott, Clare L., primary, Frenzel, Anna, primary, Villunger, Andreas, primary, and Johnstone, Ricky W., primary

Published
2023
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42. Supplementary Figures 1-8 from Deciphering the Molecular Events Necessary for Synergistic Tumor Cell Apoptosis Mediated by the Histone Deacetylase Inhibitor Vorinostat and the BH3 Mimetic ABT-737

Author

Wiegmans, Adrian P., primary, Alsop, Amber E., primary, Bots, Michael, primary, Cluse, Leonie A., primary, Williams, Steven P., primary, Banks, Kellie-Marie, primary, Ralli, Rachael, primary, Scott, Clare L., primary, Frenzel, Anna, primary, Villunger, Andreas, primary, and Johnstone, Ricky W., primary

Published
2023
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43. BRCA1 secondary splice-site mutations drive exon-skipping and PARP inhibitor resistance

Author

Nesic, Ksenija, Krais, John J., Vandenberg, Cassandra J., Wang, Yifan, Patel, Pooja, Kwan, Tanya, Lieschke, Elizabeth, Ho, Gwo-Yaw, Barker, Holly E., Bedo, Justin, Casadei, Silvia, Farrell, Andrew, Radke, Marc, Shield-Artin, Kristy, Penington, Jocelyn S., Geissler, Franziska, Zhang, Fan, Dobrovic, Alexander, Olesen, Inger, Kristeleit, Rebecca, Oza, Amit, Ratnayake, Gayanie, Traficante, Nadia, DeFazio, Anna, Bowtell, David D. L., Harding, Thomas C., Lin, Kevin, Swisher, Elizabeth M., Kondrashova, Olga, Scott, Clare L., Johnson, Neil, and Wakefield, Matthew J.

Subjects
Article
Abstract

BRCA1 splice isoforms Δ11 and Δ11q can contribute to PARP inhibitor (PARPi) resistance by splicing-out mutation-containing exons, producing truncated, partially-functional proteins. However, the clinical impact and underlying drivers of BRCA1 exon skipping remain undetermined. We analyzed nine ovarian and breast cancer patient derived xenografts (PDX) with BRCA1 exon 11 frameshift mutations for splice isoform expression and therapy response. This included a matched PDX pair derived from a patient pre-and post-chemotherapy/PARPi regimen. BRCA1 exon 11-deficient isoform expression was generally elevated in PARPi resistant PDX tumors. Two independent PDX models acquired secondary BRCA1 splice site mutations (SSMs), predicted in silico to drive exon skipping. Predictions were confirmed using qRT-PCR, RNA sequencing, western blots and BRCA1 minigene modelling. SSMs were also enriched in post-PARPi OC patient cohorts from the ARIEL2 and ARIEL4 clinical trials. We demonstrate that SSMs drive BRCA1 exon 11 skipping and PARPi resistance, and should be clinically monitored, along with frame-restoring secondary mutations.

Published
2023

44. Additional file 1 of Targeting homologous recombination deficiency in uterine leiomyosarcoma

Author

Dall, Genevieve, Vandenberg, Cassandra J., Nesic, Ksenija, Ratnayake, Gayanie, Zhu, Wenying, Vissers, Joseph H. A., Bedő, Justin, Penington, Jocelyn, Wakefield, Matthew J., Kee, Damien, Carmagnac, Amandine, Lim, Ratana, Shield-Artin, Kristy, Milesi, Briony, Lobley, Amanda, Kyran, Elizabeth L., O’Grady, Emily, Tram, Joshua, Zhou, Warren, Nugawela, Devindee, Stewart, Kym Pham, Caldwell, Reece, Papadopoulos, Lia, Ng, Ashley P., Dobrovic, Alexander, Fox, Stephen B., McNally, Orla, Power, Jeremy D., Meniawy, Tarek, Tan, Teng Han, Collins, Ian M., Klein, Oliver, Barnett, Stephen, Olesen, Inger, Hamilton, Anne, Hofmann, Oliver, Grimmond, Sean, Papenfuss, Anthony T., Scott, Clare L., and Barker, Holly E.

Abstract

Additional file 1: Supplementary Table 1. HRD mutations identified by screening uLMS from 58 individuals.

Published
2023
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45. The molecular origin and taxonomy of mucinous ovarian carcinoma

Author

Cheasley, Dane, Wakefield, Matthew J., Ryland, Georgina L., Allan, Prue E., Alsop, Kathryn, Amarasinghe, Kaushalya C., Ananda, Sumitra, Anglesio, Michael S., Au-Yeung, George, Böhm, Maret, Bowtell, David D. L., Brand, Alison, Chenevix-Trench, Georgia, Christie, Michael, Chiew, Yoke-Eng, Churchman, Michael, DeFazio, Anna, Demeo, Renee, Dudley, Rhiannon, Fairweather, Nicole, Fedele, Clare G., Fereday, Sian, Fox, Stephen B., Gilks, C Blake, Gourley, Charlie, Hacker, Neville F., Hadley, Alison M., Hendley, Joy, Ho, Gwo-Yaw, Hughes, Siobhan, Hunstman, David G., Hunter, Sally M., Jobling, Tom W., Kalli, Kimberly R., Kaufmann, Scott H., Kennedy, Catherine J., Köbel, Martin, Le Page, Cecile, Li, Jason, Lupat, Richard, McNally, Orla M., McAlpine, Jessica N., Mes-Masson, Anne-Marie, Mileshkin, Linda, Provencher, Diane M., Pyman, Jan, Rahimi, Kurosh, Rowley, Simone M., Salazar, Carolina, Samimi, Goli, Saunders, Hugo, Semple, Timothy, Sharma, Ragwha, Sharpe, Alice J., Stephens, Andrew N., Thio, Niko, Torres, Michelle C., Traficante, Nadia, Xing, Zhongyue, Zethoven, Magnus, Antill, Yoland C., Scott, Clare L., Campbell, Ian G., and Gorringe, Kylie L.

Published
2019
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47. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial

Author

Ledermann, Jonathan, Harter, Philipp, Gourley, Charlie, Friedlander, Michael, Vergote, Ignace, Rustin, Gordon, Scott, Clare L, Meier, Werner, Shapira-Frommer, Ronnie, Safra, Tamar, Matei, Daniela, Fielding, Anitra, Spencer, Stuart, Dougherty, Brian, Orr, Maria, Hodgson, Darren, Barrett, J Carl, and Matulonis, Ursula

Published
2014
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50. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma

Author

Kondrashova, Olga, Topp, Monique, Nesic, Ksenija, Lieschke, Elizabeth, Ho, Gwo-Yaw, Harrell, Maria I., Zapparoli, Giada V., Hadley, Alison, Holian, Robert, Boehm, Emma, Heong, Valerie, Sanij, Elaine, Pearson, Richard B., Krais, John J., Johnson, Neil, McNally, Orla, Ananda, Sumitra, Alsop, Kathryn, Hutt, Karla J., Kaufmann, Scott H., Lin, Kevin K., Harding, Thomas C., Traficante, Nadia, Australian Ovarian Cancer Study (AOCS), deFazio, Anna, McNeish, Iain A., Bowtell, David D., Swisher, Elizabeth M., Dobrovic, Alexander, Wakefield, Matthew J., and Scott, Clare L.

Published
2018
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