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152. A phase 2 biomarker trial of combination cediranib and olaparib in relapsed platinum (plat) sensitive and plat resistant ovarian cancer (ovca).

Author

Liu, Joyce F., primary, Barry, William Thomas, additional, Wenham, Robert Michael, additional, Wahner Hendrickson, Andrea Elisabeth, additional, Armstrong, Deborah Kay, additional, Chan, Nancy, additional, Cohn, David E., additional, Lee, Jung-min, additional, Penson, Richard T., additional, Cristea, Mihaela C., additional, Abbruzzese, James L., additional, MATSUO, KOJI, additional, Olawaiye, Alexander, additional, Farooq, Sarah, additional, Swisher, Elizabeth M., additional, Van Allen, Eliezer Mendel, additional, Shapiro, Geoffrey, additional, Kohn, Elise C., additional, Ivy, S. Percy, additional, and Matulonis, Ursula A., additional

Published
2018
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153. Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer

Author

Tucker, Douglass W., primary, Getchell, Christopher R., additional, McCarthy, Eric T., additional, Ohman, Anders W., additional, Sasamoto, Naoko, additional, Xu, Shuyun, additional, Ko, Joo Yeon, additional, Gupta, Mamta, additional, Shafrir, Amy, additional, Medina, Jamie E., additional, Lee, Jonathan J., additional, MacDonald, Lauren A., additional, Malik, Ammara, additional, Hasselblatt, Kathleen T, additional, Li, Wenjing, additional, Zhang, Hong, additional, Kaplan, Samuel J., additional, Murphy, George F., additional, Hirsch, Michelle S., additional, Liu, Joyce F., additional, Matulonis, Ursula A., additional, Terry, Kathryn L., additional, Lian, Christine G., additional, and Dinulescu, Daniela M., additional

Published
2018
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155. Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response

Author

Zervantonakis, Ioannis K., primary, Iavarone, Claudia, additional, Chen, Hsing-Yu, additional, Selfors, Laura M., additional, Palakurthi, Sangeetha, additional, Liu, Joyce F., additional, Drapkin, Ronny, additional, Matulonis, Ursula, additional, Leverson, Joel D., additional, Sampath, Deepak, additional, Mills, Gordon B., additional, and Brugge, Joan S., additional

Published
2017
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156. Abstract CT009: Targeting MUC16 with the THIOMABTM-drug conjugate DMUC4064A in patients with platinum-resistant ovarian cancer: a Phase I escalation study

Author

Liu, Joyce F., primary, Moore, Kathleen N., additional, Wang, Judy S., additional, Patel, Manish, additional, Birrer, Michael J., additional, Hamilton, Erika, additional, Barroilhet, Lisa, additional, Flanagan, William M., additional, Wang, Yulei, additional, Garg, Amit, additional, Lu, Xuyang, additional, Vaze, Anjali, additional, Amin, Dilip, additional, Leipold, Doug, additional, Commerford, S Renee, additional, Humke, Eric W., additional, and Burris, Harold A., additional

Published
2017
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157. Abstract 4033: Combined MEK and BCL-2/XL inhibition as a potential drug combination for the treatment of high-grade serous ovarian cancer

Author

Iavarone, Claudia, primary, Zervantonakis, Ioannis, additional, Selfors, Laura M., additional, Palakurthi, Sangeetha, additional, Liu, Joyce F., additional, Matulonis, Ursula A., additional, Drapkin, Ronny I., additional, Mills, Gordon B., additional, Leverson, Joel D., additional, Sampath, Deepak, additional, and Brugge, Joan S., additional

Published
2017
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158. Abstract CT008: Phase I study of the alpha specific PI3-Kinase inhibitor BYL719 and the poly (ADP-Ribose) polymerase (PARP) inhibitor olaparib in recurrent ovarian and breast cancer: Analysis of the dose escalation and ovarian cancer expansion cohort

Author

Konstantinopoulos, Panagiotis A., primary, Barry, William T., additional, Birrer, Michael, additional, Westin, Shannon N., additional, Farooq, Sarah, additional, Cadoo, Karen, additional, Whalen, Christin, additional, Luo, Weixiu, additional, Liu, Hui, additional, Aghajanian, Carol, additional, Solit, David B., additional, Mills, Gordon B., additional, Taylor, Barry S., additional, Won, Helen, additional, Berger, Michael F., additional, Palakurthi, Sangeetha, additional, Liu, Joyce F., additional, Cantley, Lew, additional, Kaufmann, Scott H., additional, Swisher, Elizabeth M., additional, D'Andrea, Alan D., additional, Winer, Eric, additional, Wulf, Gerburg M., additional, and Matulonis, Ursula A., additional

Published
2017
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159. PRKCI promotes immune suppression in ovarian cancer

Author

Sarkar, Sharmistha, primary, Bristow, Christopher A., additional, Dey, Prasenjit, additional, Rai, Kunal, additional, Perets, Ruth, additional, Ramirez-Cardenas, Alejandra, additional, Malasi, Shruti, additional, Huang-Hobbs, Emmet, additional, Haemmerle, Monika, additional, Wu, Sherry Y., additional, McGuire, Michael, additional, Protopopov, Alexei, additional, Jiang, Shan, additional, Liu, Joyce F., additional, Hirsch, Michelle S., additional, Chang, Qing, additional, Lazar, Alexander J., additional, Sood, Anil K., additional, Drapkin, Ronny, additional, DePinho, Ronald, additional, Draetta, Giulio, additional, and Chin, Lynda, additional

Published
2017
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161. Phase 2, two-group, two-stage, open-label study of avelumab in patients with microsatellite stable, microsatellite instable and POLE-mutated recurrent or persistent endometrial cancer.

Author

Konstantinopoulos, Panagiotis A., primary, Liu, Joyce F., additional, Barry, William Thomas, additional, Krasner, Carolyn N., additional, Buss, Mary K., additional, Birrer, Michael J., additional, Farooq, Sarah, additional, Campos, Susana M., additional, Stover, Elizabeth, additional, Schumer, Susan, additional, Wright, Alexi A., additional, Curtis, Jennifer, additional, Peralta, Ariana, additional, Whalen, Christin, additional, Dizon, Don S., additional, Penson, Richard T., additional, Cannistra, Stephen A., additional, Fleming, Gini F., additional, and Matulonis, Ursula A., additional

Published
2017
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162. Overall survival and updated progression-free survival results from a randomized phase 2 trial comparing the combination of olaparib and cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer.

Author

Liu, Joyce F., primary, Barry, William Thomas, additional, Birrer, Michael J., additional, Lee, Jung-min, additional, Buckanovich, Ronald J., additional, Fleming, Gini F., additional, Rimel, Bj, additional, Buss, Mary K., additional, Nattam, Sreenivasa R., additional, Hurteau, Jean, additional, Luo, Weixiu, additional, Farooq, Sarah, additional, Whalen, Christin, additional, Kohn, Elise C., additional, Ivy, S. Percy, additional, and Matulonis, Ursula A., additional

Published
2017
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164. Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics

Author

Liu, Joyce F., primary, Palakurthi, Sangeetha, additional, Zeng, Qing, additional, Zhou, Shan, additional, Ivanova, Elena, additional, Huang, Wei, additional, Zervantonakis, Ioannis K., additional, Selfors, Laura M., additional, Shen, Yiping, additional, Pritchard, Colin C., additional, Zheng, Mei, additional, Adleff, Vilmos, additional, Papp, Eniko, additional, Piao, Huiying, additional, Novak, Marian, additional, Fotheringham, Susan, additional, Wulf, Gerburg M., additional, English, Jessie, additional, Kirschmeier, Paul T., additional, Velculescu, Victor E., additional, Paweletz, Cloud, additional, Mills, Gordon B., additional, Livingston, David M., additional, Brugge, Joan S., additional, Matulonis, Ursula A., additional, and Drapkin, Ronny, additional

Published
2017
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165. Abstract PR01: Systems analysis of signaling pathway adaptation to design effective PI3K-based combination therapies using ovarian cancer patient-derived xenografts

Author

Zervantonakis, Ioannis K., primary, Iavarone, Claudia, additional, Chen, Hsing-Yu, additional, Leverson, Joel, additional, Sampath, Deepak, additional, Palakurthi, Sangeetha, additional, Drapkin, Ronny, additional, Liu, Joyce F., additional, Matulonis, Ursula, additional, Mills, Gordon, additional, and Brugge, Joan S., additional

Published
2017
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166. Randomized Phase II Trial of Seribantumab in Combination With Paclitaxel in Patients With Advanced Platinum-Resistant or -Refractory Ovarian Cancer

Author

Liu, Joyce F., primary, Ray-Coquard, Isabelle, additional, Selle, Frederic, additional, Poveda, Andrés M., additional, Cibula, David, additional, Hirte, Hal, additional, Hilpert, Felix, additional, Raspagliesi, Francesco, additional, Gladieff, Laurence, additional, Harter, Philipp, additional, Siena, Salvatore, additional, del Campo, Josep Maria, additional, Tabah-Fisch, Isabelle, additional, Pearlberg, Joseph, additional, Moyo, Victor, additional, Riahi, Kaveh, additional, Nering, Rachel, additional, Kubasek, William, additional, Adiwijaya, Bambang, additional, Czibere, Akos, additional, Naumann, R. Wendel, additional, Coleman, Robert L., additional, Vergote, Ignace, additional, MacBeath, Gavin, additional, and Pujade-Lauraine, Eric, additional

Published
2016
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168. Abstract 3843: Design of effective combination therapies for high-grade serous ovarian cancer using patient-derived xenograft models

Author

Iavarone, Claudia, primary, Zervantonakis, Ioannis, additional, Chen, Hsing-Yu, additional, Palakurthi, Sangeetha S., additional, Liu, Joyce F., additional, Matulonis, Ursula, additional, Drapkin, Ronny, additional, Mills, Gordon, additional, Leverson, Joel, additional, Sampath, Deepak, additional, and Brugge, Joan, additional

Published
2016
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169. In vivo synergism between PARP-inhibitor olaparib and HSP90-inhibitor AT13387 in high grade serous ovarian cancer patient derived xenografts.

Author

Konstantinopoulos, Panagiotis, primary, Palakurthi, Sangeetha, additional, Zeng, Qing, additional, Zhou, Shan, additional, Liu, Joyce F., additional, Ivanova, Elena, additional, Paweletz, Cloud, additional, Kommajosyula, Naveen, additional, D'Andrea, Alan D., additional, Shapiro, Geoffrey, additional, and Matulonis, Ursula A., additional

Published
2016
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171. A randomized, open-label, phase II study of anti-NaPi2b antibody-drug conjugate (ADC) lifastuzumab (Lifa) vedotin (DNIB0600A) compared to pegylated liposomal doxorubicin (PLD) in patients (pts) with platinum-resistant ovarian cancer (PROC).

Author

Banerjee, Susana N., primary, Oza, Amit M., additional, Birrer, Michael J., additional, Hamilton, Erika Paige, additional, Hasan, Jurjees, additional, Leary, Alexandra, additional, Moore, Kathleen N., additional, Mackowiak-Matejczyk, Beata, additional, Pikiel, Joanna, additional, Ray-Coquard, Isabelle, additional, Trask, Peter, additional, Lin, Kedan, additional, Vaze, Anjali, additional, Choi, YounJeong, additional, Marsters, Jim, additional, Maslyar, Daniel J., additional, Lemahieu, Vanessa, additional, Wang, Yulei, additional, Humke, Eric William, additional, and Liu, Joyce F., additional

Published
2016
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174. Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment

Author

Wang, Suming, primary, Blois, Anna, additional, El Rayes, Tina, additional, Liu, Joyce F., additional, Hirsch, Michelle S., additional, Gravdal, Karsten, additional, Palakurthi, Sangeetha, additional, Bielenberg, Diane R., additional, Akslen, Lars A., additional, Drapkin, Ronny, additional, Mittal, Vivek, additional, and Watnick, Randolph S., additional

Published
2016
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175. Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer

Author

Strickland, Kyle C., primary, Howitt, Brooke E., additional, Shukla, Sachet A., additional, Rodig, Scott, additional, Ritterhouse, Lauren L., additional, Liu, Joyce F., additional, Garber, Judy E., additional, Chowdhury, Dipanjan, additional, Wu, Catherine J., additional, D’Andrea, Alan D., additional, Matulonis, Ursula A., additional, and Konstantinopoulos, Panagiotis A., additional

Published
2016
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177. A Phase 1 trial of the PARP inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

Author

Liu, Joyce F., Tolaney, Sara M., Birrer, Michael, Fleming, Gini F., Buss, Mary K., Dahlberg, Suzanne E., Lee, Hang, Whalen, Christin, Tyburski, Karin, Winer, Eric, Ivy, Percy, and Matulonis, Ursula A.

Subjects
Adult, Diarrhea, Receptor, ErbB-2, Administration, Oral, Breast Neoplasms, Capsules, Carcinoma, Ovarian Epithelial, Poly(ADP-ribose) Polymerase Inhibitors, Article, Drug Administration Schedule, Piperazines, Antineoplastic Combined Chemotherapy Protocols, Humans, Neoplasms, Glandular and Epithelial, Fatigue, Aged, Ovarian Neoplasms, Dose-Response Relationship, Drug, Nausea, Middle Aged, Receptors, Vascular Endothelial Growth Factor, Treatment Outcome, Receptors, Estrogen, Quinazolines, Phthalazines, Female, Neoplasm Recurrence, Local, Receptors, Progesterone, Tablets
Abstract

Poly(ADP-ribose) polymerase (PARP)-inhibitors and anti-angiogenics have activity in recurrent ovarian and breast cancer; however, the effect of combined therapy against PARP and angiogenesis in this population has not been reported. We investigated the toxicities and recommended phase 2 dosing (RP2D) of the combination of cediranib, a multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR)-1/2/3 and olaparib, a PARP-inhibitor (NCT01116648).Cediranib tablets once daily and olaparib capsules twice daily were administered orally in a standard 3+3 dose escalation design. Patients with recurrent ovarian or metastatic triple-negative breast cancer were eligible. Patients had measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or met Gynecologic Cancer InterGroup (GCIG) CA125 criteria. No prior PARP-inhibitors or anti-angiogenics in the recurrent setting were allowed.28 patients (20 ovarian, 8 breast) enrolled to 4 dose levels. 2 dose limiting toxicities (DLTs) (1 grade 4 neutropenia ≥ 4 days; 1 grade 4 thrombocytopenia) occurred at the highest dose level (cediranib 30 mg daily; olaparib 400 mg twice daily [BID]). The RP2D was cediranib 30 mg daily and olaparib 200 mg BID. Grade 3 or higher toxicities occurred in 75% of patients, and included grade 3 hypertension (25%) and grade 3 fatigue (18%). One grade 3 bowel obstruction occurred. The overall response rate (ORR) in the 18 RECIST-evaluable ovarian cancer patients was 44%, with a clinical benefit rate (ORR plus stable disease (SD)24 weeks) of 61%. None of the seven evaluable breast cancer patients achieved clinical response; two patients had stable disease for24 weeks.The combination of cediranib and olaparib has haematologic DLTs and anticipated class toxicities, with promising evidence of activity in ovarian cancer patients.

Published
2013

179. A phase 2, two-stage study of avelumab and axitinib in patients with mismatch repair–proficient (MMR-P) recurrent or persistent endometrial cancer (EC).

Author

Lee, Elizabeth Katherine, Xiong, Niya, Cheng, SuChun, Polak, Madeline, Krasner, Carolyn N., Campos, Susana M., Wright, Alexi A., Liu, Joyce F., Shea, Meghan, Yeku, Oladapo O., Castro, Cesar Martin, Porter, Rebecca L, Stover, Elizabeth, Bouberhan, Sara, Moroney, John William, Penson, Richard T., Fleming, Gini F., Matulonis, Ursula A., and Konstantinopoulos, Panagiotis A.

Published
2023
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180. First-in-human phase 1/2 study of ubamatamab, a MUC16xCD3 bispecific antibody, administered alone or in combination with cemiplimab in patients with recurrent ovarian cancer.

Author

Moore, Kathleen N., Bouberhan, Sara, Hamilton, Erika P., Liu, Joyce F., O'Cearbhaill, Roisin Eilish, O'Malley, David M., Papadamitriou, Konstantinos, Schröder, David, Van Nieuwenhuysen, Els, Yoo, Suk-Young, Peterman, Mary Jane, Goncalves, Priscila Hermont, Schmidt, Tamara, Zhu, Min, Lowy, Israel, Uldrick, Thomas S., and Miller, Elizabeth

Published
2023
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182. Correlation of cyclin E1 expression and clinical outcomes in a phase 1b dose-escalation study of azenosertib (ZN-c3), a WEE1 inhibitor, in combination with chemotherapy (CT) in patients (pts) with platinum-resistant or refractory (R/R) epithelial...

Author

Liu, Joyce F., Fu, Siqing, Richardson, Gary Edward, Vranjes, Zivko, Meniawy, Tarek, Shannon, Catherine M., Hamilton, Erika P., Blank, Stephanie V., Mathews, Cara Amanda, Alidzanovic, Jasmina, Ruseva, Rossitza Krasteva, Shi, Qing, Harismendy, Olivier, Ptaszynski, Ann M., Westin, Shannon Neville, Meric-Bernstam, Funda, and Thaker, Premal H.

Published
2023
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183. Randomized phase 2 study of gemcitabine with or without ATR inhibitor berzosertib in platinum-resistant ovarian cancer: Final overall survival (OS) and biomarker analyses.

Author

Konstantinopoulos, Panagiotis A., Lee, Elizabeth Katherine, Cheng, SuChun, Da Costa, Alexandre Andre B. A., Wahner Hendrickson, Andrea Elisabeth, Gulhan, Doga, Kochupurakkal, Bose, Kolin, David, Kohn, Elise C., Liu, Joyce F., Stover, Elizabeth, Curtis, Jennifer, Sawyer, Hannah, Polak, Madeline, Chowdhury, Dipanjan, Färkkilä, Anniina, D'Andrea, Alan D., Shapiro, Geoffrey, and Matulonis, Ursula A.

Published
2023
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184. Abstract 1471: Establishment, characterization, and clinical correlation of a platform of ovarian patient-derived xenograft (PDX) models

Author

Palakurthi, Sangeetha S., primary, Liu, Joyce F., additional, Zeng, Qing, additional, Zhou, Shan, additional, Huang, Wei, additional, Ivanova, Elena, additional, Paweletz, Cloud, additional, Murgo, John R., additional, Evangelista, Justin, additional, Buttimer, Melissa, additional, Curtis, Jennifer, additional, Piao, Huiying, additional, Gokhale, Prafulla, additional, Pritchard, Colin, additional, English, Jessie M., additional, Kirschmeier, Paul, additional, Wong, Kwok-Kin, additional, Matulonis, Ursula A., additional, and Drapkin, Ronny, additional

Published
2015
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185. CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer

Author

Lee, Jung-Min, primary, Trepel, Jane B., additional, Choyke, Peter, additional, Cao, Liang, additional, Sissung, Tristan, additional, Houston, Nicole, additional, Yu, Minshu, additional, Figg, William D., additional, Turkbey, Ismail Baris, additional, Steinberg, Seth M., additional, Lee, Min-Jung, additional, Ivy, S. Percy, additional, Liu, Joyce F., additional, Matulonis, Ursula A., additional, and Kohn, Elise C., additional

Published
2015
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186. Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Target ID4

Author

Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Koch Institute for Integrative Cancer Research at MIT, Ren, Yin, von Maltzhan, Geoffrey, Agrawal, Amit, Mesirov, Jill P., Lo, Justin H., Bhatia, Sangeeta N., Cheung, Hiu Wing, Cowley, Glenn S., Weir, Barbara A., Boehm, Jesse S., Tamayo, Pablo, Karst, Alison M., Liu, Joyce F., Hirsch, Michelle S., Drapkin, Ronny, Root, David E., Fogal, Valentina, Ruoslahti, Erkki, Hahn, William C., Bhatia, Sangeeta N, Whitaker College of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Koch Institute for Integrative Cancer Research at MIT, Ren, Yin, von Maltzhan, Geoffrey, Agrawal, Amit, Mesirov, Jill P., Lo, Justin H., Bhatia, Sangeeta N., Cheung, Hiu Wing, Cowley, Glenn S., Weir, Barbara A., Boehm, Jesse S., Tamayo, Pablo, Karst, Alison M., Liu, Joyce F., Hirsch, Michelle S., Drapkin, Ronny, Root, David E., Fogal, Valentina, Ruoslahti, Erkki, Hahn, William C., and Bhatia, Sangeeta N

Abstract

The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance because many of these targets are not amenable to manipulation by small molecules or antibodies. RNA interference provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) that comprised small interfering RNA (siRNA) complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We used TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor–bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets., Howard Hughes Medical Institute, National Cancer Institute (U.S.) (Grant U54 CA119349), National Cancer Institute (U.S.) (Grant CA119335), National Cancer Institute (U.S.) (Grant R01 CA124427), Starr Cancer Consortium, Marie D. and Pierre Casimir-Lambert Fund, National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30 CA14051)

Published
2014

187. An in-tumor genetic screen reveals that the BET bromodomain protein, BRD4, is a potential therapeutic target in ovarian carcinoma

Author

Baratta, Maria Giuseppina, primary, Schinzel, Anna C., additional, Zwang, Yaara, additional, Bandopadhayay, Pratiti, additional, Bowman-Colin, Christian, additional, Kutt, Jennifer, additional, Curtis, Jennifer, additional, Piao, Huiying, additional, Wong, Laura C., additional, Kung, Andrew L., additional, Beroukhim, Rameen, additional, Bradner, James E., additional, Drapkin, Ronny, additional, Hahn, William C., additional, Liu, Joyce F., additional, and Livingston, David M., additional

Published
2014
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188. Abstract 1202: Patient derived xenograft model platform of high grade serous ovarian cancer supporting discovery of targeted therapies and biomarkers

Author

Palakurthi, Sangeetha S., primary, Liu, Joyce F., additional, Zeng, Qing, additional, Zhou, Shan, additional, Ivanova, Elena, additional, Paweletz, Cloud, additional, Murgo, John, additional, Evangelista, Justin, additional, Curtis, Jennifer, additional, Piao, Huiying, additional, Gokhale, Prafulla, additional, English, Jessie M., additional, Kirschmeier, Paul, additional, Wong, Kwok-Kin, additional, Matulonis, Ursula A., additional, and Drapkin, Ronny, additional

Published
2014
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192. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer

Author

Liu, Joyce F., primary, Tolaney, Sara M., additional, Birrer, Michael, additional, Fleming, Gini F., additional, Buss, Mary K., additional, Dahlberg, Suzanne E., additional, Lee, Hang, additional, Whalen, Christin, additional, Tyburski, Karin, additional, Winer, Eric, additional, Ivy, Percy, additional, and Matulonis, Ursula A., additional

Published
2013
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193. Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment.

Author

Suming Wang, Blois, Anna, El Rayes, Tina, Liu, Joyce F., Hirsch, Michelle S., Gravdal, Karsten, Palakurthi, Sangeetha, Bielenberg, Diane R., Akslen, Lars A., Drapkin, Ronny, Mittal, Vivek, and Watnick, Randolph S.

Subjects
THROMBOSPONDIN-1, DRUG development, OVARIAN cancer treatment, THROMBOSPONDINS, DRUG efficacy, THERAPEUTICS
Abstract

The article presents research on the development of stimulating thrombospondin-1 (TSP-1) therapeutic cyclic peptide to treat ovarian cancer through tumor microenvironment. Topics discussed include an overview of ovarian cancer and its mortality rate, its treatment through TSP-1 peptide, and the efficacy of prosaposin peptide in ovarian cancer treatment.

Published
2016
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194. Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4

Author

Ren, Yin, primary, Cheung, Hiu Wing, additional, von Maltzhan, Geoffrey, additional, Agrawal, Amit, additional, Cowley, Glenn S., additional, Weir, Barbara A., additional, Boehm, Jesse S., additional, Tamayo, Pablo, additional, Karst, Alison M., additional, Liu, Joyce F., additional, Hirsch, Michelle S., additional, Mesirov, Jill P., additional, Drapkin, Ronny, additional, Root, David E., additional, Lo, Justin, additional, Fogal, Valentina, additional, Ruoslahti, Erkki, additional, Hahn, William C., additional, and Bhatia, Sangeeta N., additional

Published
2012
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197. Anti-CCR4 monoclonal antibody enhances antitumor immunity by modulating tumor-infiltrating Tregs in an ovarian cancer xenograft humanized mouse model

Author

Chang, De-Kuan, Peterson, Eric, Sun, Jiusong, Goudie, Calum, Drapkin, Ronny I., Liu, Joyce F., Matulonis, Ursula, Zhu, Quan, and Marasco, Wayne A.

Subjects
CCR4, immunotherapy, monoclonal antibody, ovarian cancer, regulatory T cells
Abstract

Recent studies have demonstrated that regulatory T cells (Tregs) are recruited to tumor sites where they can suppress antitumor immunity. The chemokine receptor CCR4 is expressed at high levels on functional CD4+CD25+FoxP3+ Tregs and production of the CCR4 ligand CCL22 by tumor cells and tumor-associated macrophages is associated with Treg recruitment to the tumor site. Here, we tested IgG1 and IgG4 isotypes of human anti-CCR4 mAb2-3 for their in vitro activity and in vivo capacity in a NSG mouse model bearing CCL22-secreting ovarian cancer (OvCA) xenograft to modulate Tregs and restore antitumor activity. Both mAb2-3 isotypes blocked in vitro chemoattraction of Tregs to CCL22-secreting OvCA cells. However, they differed in their in vivo mode of action with IgG1 causing Treg depletion and IgG4 blocking migration to the tumors. Primary T cells that were primed with OvCA-pulsed dendritic cells (DCs) demonstrated INFγ secretion that could be enhanced through Treg depletion by mAb2-3. Humanized mice reconstructed with allogeneic tumor-primed T cells (TP-T) were used to evaluate the restoration of OvCA immunity by depletion or blockade of Tregs with mAb2-3. We observed that IgG1 was more potent than IgG4 in inhibiting tumor growth. Mechanism studies demonstrated that mAb2-3 treatment lead to inhibition of IL-2 binding to its receptor. Further studies showed that mAb2-3 induced CD25 shedding (sCD25) from Tregs which lead to a decrease in IL-2-dependent survival. Together, the results demonstrate that mAb2-3 is an agonist antibody that can restore anti-OvCA immunity through modulation of Treg activity.

Published
2016
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198. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance.

Author

Johnsonq, Neil, Johnson, Shawn F., Wei Yao, Yu-Chen Li, Young-Eun Choi, Bernhardy, Andrea J., Yifa Wang, Capelletti, Marzia, Sarosiek, Kristopher A., Moreau, Lisa A., Chowdhury, Dipanjan, Wickramanayake, Anneka, Harrell, Maria I., Liu, Joyce F., D'Andrea, Alan D., Miron, Alexander, Swisher, Elizabeth M., and Shapiro, Geoffrey I.

Subjects
BREAST cancer research, MUTANT proteins, CELL lines, ADENOSINE diphosphate, POLYMERASES, CANCER research
Abstract

The article reports on a study conducted to examine the stabilization of mutant Breast Cancer Type 1 Susceptibility Protein (BRCA1). It mentions that MDA-MB-436, breast cancer cell line, was cultured in presence of poly adenosine (ADP)-ribose polymerase (PARP) inhibitor rucaparib. The study found that HSP90 interacts with and stabilizes mutant BRCA1 proteins under PARP inhibitor selection pressure and a BRCT domain-mutated BRCA1 protein showed a partial function.

Published
2013
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200. Treatment of Recurrent Platinum-Sensitive Epithelial Ovarian Cancer.

Author

Liu, Joyce F. and Matulonis, Ursula A.

Subjects
*OVARIAN cancer, *CANCER in women, *CANCER treatment, *CANCER relapse, *DRUG therapy, *CLINICAL trials, *ONCOLOGY, *DISEASE management, *MEDICAL research
Abstract

Ovarian cancer remains a leading cause of cancer death among women, with an estimated 125000 deaths worldwide. Newly diagnosed ovarian cancer is very responsive to first-line platinum-based therapy, but the majority of patients will have disease recurrence. Patients in whom disease recurs more than 6 months after completing prior platinum-based treatment are considered to have platinum-sensitive disease, and questions remain regarding the optimal management of their disease. Many options exist for these patients, including systemic chemotherapy, and in specific circumstances, secondary cytoreductive surgery or radioablative techniques can be considered for patients with localized recurrences and long disease-free intervals. For patients receiving systemic chemotherapy, data from clinical trials suggest that combination platinum-based chemotherapy should be considered in this setting for patients in whom the toxicities would be acceptable, although the optimal regimen remains unclear. Ongoing investigations seek to address the role of secondary cytoreductive surgery, the optimal therapy for recurrent platinum-sensitive disease, the therapeutic potential of non-platinum-based therapies, and the role of biological therapy in this setting. [ABSTRACT FROM AUTHOR]

Published
2010

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