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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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4. Preclinical evaluation of FAP-2286 for fibroblast activation protein targeted radionuclide imaging and therapy

Author

Zboralski, Dirk, Hoehne, Aileen, Bredenbeck, Anne, Schumann, Anne, Nguyen, Minh, Schneider, Eberhard, Ungewiss, Jan, Paschke, Matthias, Haase, Christian, von Hacht, Jan L., Kwan, Tanya, Lin, Kevin K., Lenore, Jan, Harding, Thomas C., Xiao, Jim, Simmons, Andrew D., Mohan, Ajay-Mohan, Beindorff, Nicola, Reineke, Ulrich, Smerling, Christiane, and Osterkamp, Frank

Published
2022
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6. Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer

Author

Shah, Khyati N, Bhatt, Roma, Rotow, Julia, Rohrberg, Julia, Olivas, Victor, Wang, Victoria E, Hemmati, Golzar, Martins, Maria M, Maynard, Ashley, Kuhn, Jonathan, Galeas, Jacqueline, Donnella, Hayley J, Kaushik, Swati, Ku, Angel, Dumont, Sophie, Krings, Gregor, Haringsma, Henry J, Robillard, Liliane, Simmons, Andrew D, Harding, Thomas C, McCormick, Frank, Goga, Andrei, Blakely, Collin M, Bivona, Trever G, and Bandyopadhyay, Sourav

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Lung, Cancer, Lung Cancer, 5.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Good Health and Well Being, Animals, Apoptosis, Aurora Kinase A, Cell Count, Cell Cycle Proteins, Cell Line, Tumor, Drug Resistance, Neoplasm, ErbB Receptors, Humans, Lung Neoplasms, Mice, Microtubule-Associated Proteins, Mutation, Neoplasm, Residual, Nuclear Proteins, Phosphorylation, Protein Kinase Inhibitors, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance.

Published
2019

7. A Quantitative Chemotherapy Genetic Interaction Map Reveals Factors Associated with PARP Inhibitor Resistance.

Author

Hu, Hsien-Ming, Zhao, Xin, Kaushik, Swati, Robillard, Lilliane, Barthelet, Antoine, Lin, Kevin K, Shah, Khyati N, Simmons, Andy D, Raponi, Mitch, Harding, Thomas C, and Bandyopadhyay, Sourav

Subjects
Cell Line, Tumor, Humans, Neoplasms, Ovarian Neoplasms, Cisplatin, Blood Proteins, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors, Antineoplastic Agents, DNA Repair, RNA Interference, Drug Synergism, Drug Resistance, Neoplasm, Female, Gene Regulatory Networks, Homologous Recombination, Poly(ADP-ribose) Polymerase Inhibitors, DNA repair, biomarkers, breast cancer, chemotherapy, genetic interactions, ovarian cancer, synthetic lethality, Cell Line, Tumor, Drug Resistance, Neoplasm, Biochemistry and Cell Biology, Medical Physiology
Abstract

Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations. We identify that ARID1A loss confers resistance to PARP inhibitors in cells and ovarian cancer patients and that loss of GPBP1 causes resistance to cisplatin and PARP inhibitors through the regulation of genes involved in homologous recombination. This map helps navigate patient genomic data and optimize chemotherapeutic regimens by delineating factors involved in the response to specific types of DNA damage.

Published
2018

8. 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

10. 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

12. 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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14. 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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15. Supplementary Figure 8 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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16. 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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17. Supplementary Figure 9 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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18. 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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19. Supplementary Tables 1 through 4 and Supplementary Figures 1 through 5 from In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing

Author

Tjin Tham Sjin, Robert, primary, Lee, Kwangho, primary, Walter, Annette O., primary, Dubrovskiy, Aleksandr, primary, Sheets, Michael, primary, Martin, Thia St., primary, Labenski, Matthew T., primary, Zhu, Zhendong, primary, Tester, Richland, primary, Karp, Russell, primary, Medikonda, Aravind, primary, Chaturvedi, Prasoon, primary, Ren, Yixuan, primary, Haringsma, Henry, primary, Etter, Jeff, primary, Raponi, Mitch, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Westlin, William F., primary, Petter, Russell C., primary, Allen, Andrew, primary, and Singh, Juswinder, primary

Published
2023
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20. Supplementary Figure 2 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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21. Data from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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22. 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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23. Supplementary Materials and Methods from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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24. Supplementary Figure 7 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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25. Supplementary Figure 11 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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26. Supplementary Figure 3 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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27. 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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28. Supplementary Table 2 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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29. Supplementary Table 1 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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30. Supplementary Table 3 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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31. Supplementary Materials and Methods and Supplementary Figure Legends from In Vitro and In Vivo Characterization of Irreversible Mutant-Selective EGFR Inhibitors That Are Wild-Type Sparing

Author

Tjin Tham Sjin, Robert, primary, Lee, Kwangho, primary, Walter, Annette O., primary, Dubrovskiy, Aleksandr, primary, Sheets, Michael, primary, Martin, Thia St., primary, Labenski, Matthew T., primary, Zhu, Zhendong, primary, Tester, Richland, primary, Karp, Russell, primary, Medikonda, Aravind, primary, Chaturvedi, Prasoon, primary, Ren, Yixuan, primary, Haringsma, Henry, primary, Etter, Jeff, primary, Raponi, Mitch, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Westlin, William F., primary, Petter, Russell C., primary, Allen, Andrew, primary, and Singh, Juswinder, primary

Published
2023
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32. Supplementary Figure 4 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, 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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35. Supplementary Figure 5 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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36. Supplementary Figure 6 from Discovery of a Mutant-Selective Covalent Inhibitor of EGFR that Overcomes T790M-Mediated Resistance in NSCLC

Author

Walter, Annette O., primary, Sjin, Robert Tjin Tham, primary, Haringsma, Henry J., primary, Ohashi, Kadoaki, primary, Sun, Jing, primary, Lee, Kwangho, primary, Dubrovskiy, Aleksandr, primary, Labenski, Matthew, primary, Zhu, Zhendong, primary, Wang, Zhigang, primary, Sheets, Michael, primary, St Martin, Thia, primary, Karp, Russell, primary, van Kalken, Dan, primary, Chaturvedi, Prasoon, primary, Niu, Deqiang, primary, Nacht, Mariana, primary, Petter, Russell C., primary, Westlin, William, primary, Lin, Kevin, primary, Jaw-Tsai, Sarah, primary, Raponi, Mitch, primary, Van Dyke, Terry, primary, Etter, Jeff, primary, Weaver, Zoe, primary, Pao, William, primary, Singh, Juswinder, primary, Simmons, Andrew D., primary, Harding, Thomas C., primary, and Allen, Andrew, primary

Published
2023
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38. Supplementary Data from K562/GM-CSF Immunotherapy Reduces Tumor Burden in Chronic Myeloid Leukemia Patients with Residual Disease on Imatinib Mesylate

Author

Smith, B. Douglas, primary, Kasamon, Yvette L., primary, Kowalski, Jeanne, primary, Gocke, Christopher, primary, Murphy, Kathleen, primary, Miller, Carole B., primary, Garrett-Mayer, Elizabeth, primary, Tsai, Hua-Ling, primary, Qin, Lu, primary, Chia, Christina, primary, Biedrzycki, Barbara, primary, Harding, Thomas C., primary, Tu, Guang Haun, primary, Jones, Richard, primary, Hege, Kristen, primary, and Levitsky, Hyam I., primary

Published
2023
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39. 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

40. 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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42. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

Author

van den Eertwegh, Alfons JM, Versluis, Jurjen, van den Berg, H Pieter, Santegoets, Saskia JAM, van Moorselaar, R Jeroen A, van der Sluis, Tim M, Gall, Helen E, Harding, Thomas C, Jooss, Karin, Lowy, Israel, Pinedo, Herbert M, Scheper, Rik J, Stam, Anita GM, von Blomberg, B Mary E, de Gruijl, Tanja D, Hege, Kristen, Sacks, Natalie, and Gerritsen, Winald R

Published
2012
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43. Correction: Corrigendum: Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients

Author

Chabon, Jacob J., Simmons, Andrew D., Lovejoy, Alexander F., Esfahani, Mohammad S., Newman, Aaron M., Haringsma, Henry J., Kurtz, David M., Stehr, Henning, Scherer, Florian, Karlovich, Chris A., Harding, Thomas C., Durkin, Kathleen A., Otterson, Gregory A., Thomas Purcell, W., Ross Camidge, D., Goldman, Jonathan W., Sequist, Lecia V., Piotrowska, Zofia, Wakelee, Heather A., Neal, Joel W., Alizadeh, Ash A., and Diehn, Maximilian

Published
2016
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44. Abstract LBA032: Pan-cancer analysis of fibroblast activation protein alpha (FAP) expression to guide tumor selection for the peptide-targeted radionuclide therapy FAP-2286

Author

Kwan, Tanya T., primary, Nguyen, Minh, additional, Zboralski, Dirk, additional, Schumann, Anne, additional, Bredenbeck, Anne, additional, Paschke, Matthias, additional, Haase, Christian, additional, Hoehne, Aileen, additional, Reineke, Ulrich, additional, Smerling, Christiane, additional, Osterkamp, Frank, additional, Xiao, Jim, additional, Simmons, Andrew D., additional, Harding, Thomas C., additional, and Lin, Kevin L., additional

Published
2021
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45. Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance

Author

Hurley, Rachel M, primary, McGehee, Cordelia D, additional, Nesic, Ksenija, additional, Correia, Cristina, additional, Weiskittel, Taylor M, additional, Kelly, Rebecca L, additional, Venkatachalam, Annapoorna, additional, Hou, Xiaonan, additional, Pathoulas, Nicholas M, additional, Meng, X Wei, additional, Kondrashova, Olga, additional, Radke, Marc R, additional, Schneider, Paula A, additional, Flatten, Karen S, additional, Peterson, Kevin L, additional, Becker, Marc A, additional, Wong, Ee Ming, additional, Southey, Melissa S, additional, Dobrovic, Alexander, additional, Lin, Kevin K, additional, Harding, Thomas C, additional, McNeish, Iain, additional, Ross, Christian A, additional, Wagner, Jill M, additional, Wakefield, Matthew J, additional, Scott, Clare L, additional, Haluska, Paul, additional, Wahner Hendrickson, Andrea E, additional, Karnitz, Larry M, additional, Swisher, Elizabeth M, additional, Li, Hu, additional, Weroha, S John, additional, and Kaufmann, Scott H, additional

Published
2021
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46. Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance

Author

Hurley, Rachel M, McGehee, Cordelia D, Nesic, Ksenija, Correia, Cristina, Weiskittel, Taylor M, Kelly, Rebecca L, Venkatachalam, Annapoorna, Hou, Xiaonan, Pathoulas, Nicholas M, Meng, X Wei, Kondrashova, Olga, Radke, Marc R, Schneider, Paula A, Flatten, Karen S, Peterson, Kevin L, Becker, Marc A, Wong, Ee Ming, Southey, Melissa S, Dobrovic, Alexander, Lin, Kevin K, Harding, Thomas C, McNeish, Iain, Ross, Christian A, Wagner, Jill M, Wakefield, Matthew J, Scott, Clare L, Haluska, Paul, Hendrickson, Andrea E Wahner, Karnitz, Larry M, Swisher, Elizabeth M, Li, Hu, Weroha, S John, and Kaufmann, Scott H

Subjects
Uncategorized
Abstract

Acquired PARP inhibitor (PARPi) resistance in BRCA1- or BRCA2-mutant ovarian cancer often results from secondary mutations that restore expression of functional protein. RAD51C is a less commonly studied ovarian cancer susceptibility gene whose promoter is sometimes methylated, leading to homologous recombination (HR) deficiency and PARPi sensitivity. For this study, the PARPi-sensitive patient-derived ovarian cancer xenograft PH039, which lacks HR gene mutations but harbors RAD51C promoter methylation, was selected for PARPi resistance by cyclical niraparib treatment in vivo. PH039 acquired PARPi resistance by the third treatment cycle and grew through subsequent treatment with either niraparib or rucaparib. Transcriptional profiling throughout the course of resistance development showed widespread pathway level changes along with a marked increase in RAD51C mRNA, which reflected loss of RAD51C promoter methylation. Analysis of ovarian cancer samples from the ARIEL2 Part 1 clinical trial of rucaparib monotherapy likewise indicated an association between loss of RAD51C methylation prior to on-study biopsy and limited response. Interestingly, the PARPi resistant PH039 model remained platinum sensitive. Collectively, these results not only indicate that PARPi treatment pressure can reverse RAD51C methylation and restore RAD51C expression, but also provide a model for studying the clinical observation that PARPi and platinum sensitivity are sometimes dissociated.

Published
2021
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48. Characterization of aRAD51C-Silenced High Grade Serous Ovarian Cancer Model During PARP Inhibitor Resistance Development

Author

Hurley, Rachel M., primary, McGehee, Cordelia D., additional, Nesic, Ksenija, additional, Correia, Cristina, additional, Weiskittel, Taylor M., additional, Kelly, Rebecca L., additional, Venkatachalam, Annapoorna, additional, Hou, Xiaonan, additional, Pathoulas, Nicholas M., additional, Meng, X. Wei, additional, Kondrashova, Olga, additional, Radke, Marc R., additional, Schneider, Paula A., additional, Flatten, Karen S., additional, Peterson, Kevin L., additional, Dobrovic, Alexander, additional, Lin, Kevin K., additional, Harding, Thomas C, additional, McNeish, Iain A., additional, Ross, Christian A., additional, Wagner, Jill M., additional, Wakefield, Matthew J., additional, Scott, Clare L., additional, Haluska, Paul, additional, Wahner Hendrickson, Andrea E., additional, Karnitz, Larry M., additional, Swisher, Elizabeth M., additional, Li, Hu, additional, Weroha, S. John, additional, and Kaufmann, Scott H., additional

Published
2020
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49. BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer

Author

Lui, Goldie Y.L., primary, Shaw, Reid, additional, Schaub, Franz X., additional, Stork, Isabella N., additional, Gurley, Kay E., additional, Bridgwater, Caroline, additional, Diaz, Robert L., additional, Rosati, Rachele, additional, Swan, Hallie A., additional, Ince, Tan A., additional, Harding, Thomas C., additional, Gadi, Vijayakrishna K., additional, Goff, Barbara A., additional, Kemp, Christopher J., additional, Swisher, Elizabeth M., additional, and Grandori, Carla, additional

Published
2020
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