Search

Your search keyword '"Westin, Shannon N"' showing total 808 results
Start Over Author "Westin, Shannon N"
808 results on '"Westin, Shannon N"'

4. Author Correction: Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, Rodriguez, Emma, Hussain, Zulekha, Neelapu, Sattva S., Wang, Jennifer, Shah, Amishi Y., Tannir, Nizar M., Campbell, Matthew T., Gibbons, Don L., Cascone, Tina, Lu, Charles, Blumenschein, George R., Altan, Mehmet, Lim, Bora, Valero, Vincente, Loghin, Monica E., Tu, Janet, Westin, Shannon N., Naing, Aung, Garcia-Manero, Guillermo, Abdel-Wahab, Noha, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2024
Full Text
View/download PDF

5. ASO Visual Abstract: Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent—Final Results from a Phase 2 Study

Author

Wagner, Patrick, Levine, Edward A., Kim, Alex C., Shen, Perry, Fleming, Nicole D., Westin, Shannon N., Berry, Laurel K., Karakousis, Giorgos C., Tanyi, Janos L., Olson, Madeline T., Madajewski, Brian, Ostrander, Brian, Krishnan, Kartik, Balch, Charles M., and Bartlett, David L.

Published
2024
Full Text
View/download PDF

6. UBA1 inhibition sensitizes cancer cells to PARP inhibitors

Author

Awasthi, Sharad, Dobrolecki, Lacey E., Sallas, Christina, Zhang, Xudong, Li, Yang, Khazaei, Sima, Ghosh, Sumanta, Jeter, Collene R., Liu, Jinsong, Mills, Gordon B., Westin, Shannon N., Lewis, Michael T., Peng, Weiyi, Sood, Anil K., Yap, Timothy A., Yi, S. Stephen, McGrail, Daniel J., and Sahni, Nidhi

Published
2024
Full Text
View/download PDF

7. Results of a randomized phase II trial of paclitaxel and carboplatin versus bleomycin, etoposide and cisplatin for newly diagnosed and recurrent Chemonaive stromal ovarian tumors: An NRG oncology/gynecologic oncology group study14

Author

Brown, Jubilee, Miller, Austin, Holman, Laura L., Backes, Floor, Nagel, Christa, Bender, David, Miller, David S., Powell, Matthew A., Westin, Shannon N., Bonebrake, Albert, Muller, Carolyn Y., Secord, Angeles Alvarez, Crane, Erin, Schorge, John, Tew, William P., Sood, Anil K., Bookman, Michael A., Aghajanian, Carol, and Gershenson, David M.

Published
2024
Full Text
View/download PDF

11. Quality-adjusted survival in women with gynecologic malignancies receiving IMRT after surgery: A Ppatient Rreported Ooutcome study of NRG oncology's RTOG 1203

Author

Konski, Andre, Deshmukh, Snehal, Klopp, Ann H., Yeung, Anamaria R., Westin, Shannon N., Thompson, J. Spencer, Doncals, Desiree E., Cantuaria, Guilherme H.C., D'Souza, David P., Chang, Amy, Kundapur, Vijayananda, Mohan, Dasarahally S., Haas, Michael L., Kim, Yong Bae, Ferguson, Catherine L., Pugh, Stephanie L., Kachnic, Lisa A., and Bruner, Deborah W.

Published
2023
Full Text
View/download PDF

12. Improvement in Patient-Reported Outcomes With Intensity-Modulated Radiotherapy (RT) Compared With Standard RT: A Report From the NRG Oncology RTOG 1203 Study.

Author

Yeung, Anamaria R, Pugh, Stephanie L, Klopp, Ann H, Gil, Karen M, Wenzel, Lari, Westin, Shannon N, Gaffney, David K, Small, William, Thompson, Spencer, Doncals, Desiree E, Cantuaria, Guilherme HC, Yaremko, Brian P, Chang, Amy, Kundapur, Vijayananda, Mohan, Dasarahally S, Haas, Michael L, Kim, Yong Bae, Ferguson, Catherine L, Deshmukh, Snehal, Bruner, Deborah W, and Kachnic, Lisa A

Subjects
Clinical Research, Clinical Trials and Supportive Activities, Chronic Pain, Digestive Diseases, Cancer, Pain Research, Patient Safety, Female, Humans, Male, Patient Reported Outcome Measures, Radiotherapy, Intensity-Modulated, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeIn oncology trials, the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) is the standard tool for reporting adverse events (AEs), but it may underreport symptoms experienced by patients. This analysis of the NRG Oncology RTOG 1203 compared symptom reporting by patients and clinicians during radiotherapy (RT).Patients and methodsPatients with cervical or endometrial cancer requiring postoperative RT were randomly assigned to standard 4-field RT or intensity-modulated RT (IMRT). Patients completed the 6-item patient-reported outcomes version of the CTCAE (PRO-CTCAE) for GI toxicity assessing abdominal pain, diarrhea, and fecal incontinence at various time points. Patients reported symptoms on a 5-point scale. Clinicians recorded these AEs as CTCAE grades 1 to 5. Clinician- and patient-reported AEs were compared using McNemar's test for rates > 0%.ResultsOf 278 eligible patients, 234 consented and completed the PRO-CTCAE. Patients reported high-grade abdominal pain 19.1% (P < .0001), high-grade diarrhea 38.5% (P < .0001), and fecal incontinence 6.8% more frequently than clinicians. Similar effects were seen between grade ≥ 1 CTCAE toxicity and any-grade patient-reported toxicity. Between-arm comparison of patient-reported high-grade AEs revealed that at 5 weeks of RT, patients who received IMRT experienced fewer GI AEs than patients who received 4-field pelvic RT with regard to frequency of diarrhea (18.2% difference; P = .01), frequency of fecal incontinence (8.2% difference; P = .01), and interference of fecal incontinence (8.5% difference; P = .04).ConclusionPatient-reported AEs showed a reduction in symptoms with IMRT compared with standard RT, whereas clinician-reported AEs revealed no difference. Clinicians also underreported symptomatic GI AEs compared with patients. This suggests that patient-reported symptomatic AEs are important to assess in this disease setting.

Published
2020

14. Targeting the ALK–CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex

Author

Chu, Yu-Yi, Chen, Mei-Kuang, Wei, Yongkun, Lee, Heng-Huan, Xia, Weiya, Wang, Ying-Nai, Yam, Clinton, Hsu, Jennifer L., Wang, Hung-Ling, Chang, Wei-Chao, Yamaguchi, Hirohito, Jiang, Zhou, Liu, Chunxiao, Li, Ching-Fei, Nie, Lei, Chan, Li-Chuan, Gao, Yuan, Wang, Shao-Chun, Liu, Jinsong, Westin, Shannon N., Lee, Sanghoon, Sood, Anil K., Yang, Liuqing, Hortobagyi, Gabriel N., Yu, Dihua, and Hung, Mien-Chie

Published
2022
Full Text
View/download PDF

16. Contributors

Author

Backes, Floor J., primary, Beffa, Lindsey B., additional, Billingsley, Caroline C., additional, Birrer, Michael J., additional, Bixel, Kristin, additional, Boitano, Teresa K.L., additional, Brewster, Wendy R., additional, Chase, Dana M., additional, Bruce, Shaina, additional, Crown, Angelena, additional, Chu, Christina S., additional, Clarke-Pearson, Daniel L., additional, Ross, Robert A., additional, Crosland, Brian, additional, Cohen, Joshua G., additional, Coleman, Robert L., additional, DiSilvestro, Paul A., additional, Dorigo, Oliver, additional, Duska, Linda R., additional, Eskander, Ramez Nassef, additional, Gemignani, Mary L., additional, Gunderson, Camille Catherine, additional, Hagemann, Andrea R., additional, Herzog, Thomas J., additional, Korenaga, Travis R., additional, Huh, Warner K., additional, Kuroki, Lindsay, additional, Kurnit, Katherine, additional, Mannel, Robert S., additional, Massad, L. Stewart, additional, Mathews, Cara A., additional, Miller, David S., additional, Monk, Bradley J., additional, Mutch, David G., additional, Nikam, Rachita, additional, Pinkerton, JoAnn V., additional, Powell, Matthew, additional, Rash, Dominique L., additional, Landrum, Lisa M., additional, Ring, Kari L., additional, Renz, Malte, additional, Roane, Brandon, additional, Rubin, Stephen C., additional, Salani, Ritu, additional, Satero, Jane, additional, Sood, Anil K., additional, Soper, John T., additional, Stock, Elizabeth Christina, additional, Sung, C. James, additional, Tewari, Krishnansu Sujata, additional, Toboni, Michael D., additional, Tucker, Katherine, additional, Walker, Joan L., additional, Wall, Jaclyn A., additional, Washington, Christina, additional, Wenzel, Lari B., additional, Westin, Shannon N., additional, Yashar, Catheryn M., additional, Creasman, William T., additional, and Zuna, Rosemary E., additional

Published
2023
Full Text
View/download PDF

18. Exploiting metabolic vulnerabilities after anti-VEGF antibody therapy in ovarian cancer

Author

Glassman, Deanna, Kim, Mark S., Spradlin, Meredith, Badal, Sunil, Taki, Mana, Bhattacharya, Pratip, Dutta, Prasanta, Kingsley, Charles V., Foster, Katherine I., Animasahun, Olamide, Jeon, Jin Heon, Achreja, Abhinav, Jayaraman, Anusha, Kumar, Praveen, Nenwani, Minal, Wuchu, Fulei, Bayraktar, Emine, Wu, Yutuan, Stur, Elaine, Mangala, Lingegowda, Lee, Sanghoon, Yap, Timothy A., Westin, Shannon N., Eberlin, Livia S., Nagrath, Deepak, and Sood, Anil K.

Published
2023
Full Text
View/download PDF

19. Selinexor in combination with weekly paclitaxel in patients with metastatic solid tumors: Results of an open label, single-center, multi-arm phase 1b study with expansion phase in ovarian cancer

Author

Westin, Shannon N., Fu, Siqing, Tsimberidou, Apostolia, Piha-Paul, Sarina, Akhmedzhanov, Fechukwu, Yilmaz, Bulent, McQuinn, Lacey, Brink, Amanda L., Gong, Jing, Leung, Cheuk Hong, Lin, Heather, Hong, David S., Pant, Shubham, Carter, Brett, Jazaeri, Amir, Gershenson, David, Sood, Anil K., Coleman, Robert L., Shah, Jatin, Meric-Bernstam, Funda, and Naing, Aung

Published
2023
Full Text
View/download PDF

20. Expanded validation of the EPIC bowel and urinary domains for use in women with gynecologic cancer undergoing postoperative radiotherapy

Author

Gil, Karen M, Pugh, Stephanie L, Klopp, Ann H, Yeung, Anamaria R, Wenzel, Lari, Westin, Shannon N, Gaffney, David K, Small, William, Thompson, Spencer, Doncals, Desiree E, Cantuaria, Guilherme HC, Yaremko, Brian P, Chang, Amy, Kundapur, Vijayananda, Mohan, Dasarahally S, Haas, Michael L, Kim, Yong Bae, Ferguson, Catherine L, Deshmukh, Snehal, Kachnic, Lisa A, and Bruner, Deborah W

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Aging, Prostate Cancer, Urologic Diseases, Cancer, Patient Safety, 7.1 Individual care needs, Management of diseases and conditions, Adult, Aged, Aged, 80 and over, Endometrial Neoplasms, Female, Humans, Hysterectomy, Intestinal Diseases, Intestines, Middle Aged, Patient Reported Outcome Measures, Postoperative Care, Quality of Life, Radiation Injuries, Radiotherapy, Intensity-Modulated, Reproducibility of Results, Urethra, Uterine Cervical Neoplasms, Bowel and urinary toxicity, Pelvic radiation, Cervical and endometrial cancer, Patient reported outcomes, Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis, Reproductive medicine
Abstract

ObjectiveWomen with endometrial or cervical cancer at risk for recurrence receive postoperative radiation therapy (RT). A patient reported outcomes (PRO) instrument to assess bowel and urinary toxicities is the Expanded Prostate Cancer Index Composite (EPIC), which has been validated in men with prostate cancer. As this instrument specifically measures bowel toxicity and the degree to which this is a problem, it was used in NRG Oncology/RTOG 1203 to compare intensity modulated RT (IMRT) to standard RT. This paper reports on the expanded validation of EPIC for use in women receiving pelvic RT.MethodsIn addition to the EPIC bowel domain, urinary toxicity (EPIC urinary domain), patient reported bowel toxicities (PRO-CTCAE) and quality of life (Functional Assessment of Cancer Therapy (FACT)) were completed before, during and after treatment. Sensitivity, reliability and concurrent validity were assessed.ResultsMean bowel and urinary scores among 278 women enrolled were significantly worse during treatment and differed between groups. Acceptable to good reliability for bowel and urinary domain scores were obtained at all time points with the exception of one at baseline. Correlations between function and bother scores within the bowel and urinary domains were consistently stronger than those across domains. Correlations between bowel domain scores and PRO-CTCAE during treatment were stronger than those with the FACT.ConclusionCorrelations within and among the instruments indicate EPIC bowel and urinary domains are measuring conceptually discrete components of health. These EPIC domains are valid, reliable and sensitive instruments to measure PRO among women undergoing pelvic radiation.

Published
2019

24. Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2022
Full Text
View/download PDF

27. Clinical analysis of pathologic complete responders in advanced-stage ovarian cancer

Author

LaFargue, Christopher J., Handley, Katelyn F., Fleming, Nicole D., Nick, Alpa M., Chelariu-Raicu, Anca, Fellman, Bryan, Castellano, Tara, Ogasawara, Aiko, Hom-Tedla, Marianne, Blake, Erin A., da Costa, Alexandre A.B.A., Crim, Aleia K., Rauh-Hain, Alejandro, Westin, Shannon N., Coleman, Robert L., Matsuo, Koji, Baiocchi, Glauco, Hasegawa, Kosei, Moore, Kathleen, and Sood, Anil K.

Published
2022
Full Text
View/download PDF

29. Patient-Reported Toxicity During Pelvic Intensity-Modulated Radiation Therapy: NRG Oncology-RTOG 1203.

Author

Klopp, Ann H, Yeung, Anamaria R, Deshmukh, Snehal, Gil, Karen M, Wenzel, Lari, Westin, Shannon N, Gifford, Kent, Gaffney, David K, Small, William, Thompson, Spencer, Doncals, Desiree E, Cantuaria, Guilherme HC, Yaremko, Brian P, Chang, Amy, Kundapur, Vijayananda, Mohan, Dasarahally S, Haas, Michael L, Kim, Yong Bae, Ferguson, Catherine L, Pugh, Stephanie L, Kachnic, Lisa A, and Bruner, Deborah W

Subjects
Urologic Diseases, Cancer, Clinical Research, Digestive Diseases, 7.1 Individual care needs, Management of diseases and conditions, Endometrial Neoplasms, Female, Humans, Patient Reported Outcome Measures, Pelvis, Radiation Injuries, Radiotherapy, Radiotherapy, Intensity-Modulated, Uterine Cervical Neoplasms, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Purpose NRG Oncology/RTOG 1203 was designed to compare patient-reported acute toxicity and health-related quality of life during treatment with standard pelvic radiation or intensity-modulated radiation therapy (IMRT) in women with cervical and endometrial cancer. Methods Patients were randomly assigned to standard four-field radiation therapy (RT) or IMRT radiation treatment. The primary end point was change in patient-reported acute GI toxicity from baseline to the end of RT, measured with the bowel domain of the Expanded Prostate Cancer Index Composite (EPIC). Secondary end points included change in patient-reported urinary toxicity, change in GI toxicity measured with the Patient-Reported Outcome Common Terminology Criteria for Adverse Events, and quality of life measured with the Trial Outcome Index. Results From 2012 to 2015, 289 patients were enrolled, of whom 278 were eligible. Between baseline and end of RT, the mean EPIC bowel score declined 23.6 points in the standard RT group and 18.6 points in the IMRT group ( P = .048), the mean EPIC urinary score declined 10.4 points in the standard RT group and 5.6 points in the IMRT group ( P = .03), and the mean Trial Outcome Index score declined 12.8 points in the standard RT group and 8.8 points in the IMRT group ( P = .06). At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea ( P = .01), and more patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04). Conclusion Pelvic IMRT was associated with significantly less GI and urinary toxicity than standard RT from the patient's perspective.

Published
2018

30. Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy

Author

Kim, Sang T., Chu, Yanshuo, Misoi, Mercy, Suarez-Almazor, Maria E., Tayar, Jean H., Lu, Huifang, Buni, Maryam, Kramer, Jordan, Rodriguez, Emma, Hussain, Zulekha, Neelapu, Sattva S., Wang, Jennifer, Shah, Amishi Y., Tannir, Nizar M., Campbell, Matthew T., Gibbons, Don L., Cascone, Tina, Lu, Charles, Blumenschein, George R., Altan, Mehmet, Lim, Bora, Valero, Vincente, Loghin, Monica E., Tu, Janet, Westin, Shannon N., Naing, Aung, Garcia-Manero, Guillermo, Abdel-Wahab, Noha, Tawbi, Hussein A., Hwu, Patrick, Oliva, Isabella C. Glitza, Davies, Michael A., Patel, Sapna P., Zou, Jun, Futreal, Andrew, Diab, Adi, Wang, Linghua, and Nurieva, Roza

Published
2022
Full Text
View/download PDF

31. Clinical and genomic landscape of RAS mutations in gynecologic cancers

Author

Son, Ji, primary, Zhang, Yingao, additional, Lin, Heather, additional, Mirallas, Oriol, additional, Alvarez Ballesteros, Pablo, additional, Nardo, Mirella, additional, Clark, Natalie, additional, Hillman, R. Tyler, additional, Campbell, Erick, additional, Holla, Vijaykumar, additional, Johnson, Amber M., additional, Biter, Amadeo B., additional, Yuan, Ying, additional, Cobb, Lauren P., additional, Gershenson, David M., additional, Jazaeri, Amir A., additional, Lu, Karen H., additional, Soliman, Pamela T., additional, Westin, Shannon N., additional, Euscher, Elizabeth D., additional, Lawson, Barrett C., additional, Yang, Richard K., additional, Meric-Bernstam, Funda, additional, and Hong, David S., additional

Published
2024
Full Text
View/download PDF

37. List of contributors

Author

Advincula, Arnold P., primary, Bakkum-Gamez, Jamie N., additional, Bouchard-Fortier, Genevieve, additional, Burke, Anne, additional, Clark, Leslie H., additional, Coleman, Robert L., additional, Covens, Allan, additional, Cowley, Deborah S., additional, Davis, Anne R., additional, Dolan, Mary Segars, additional, Dotters-Katz, Sarah K., additional, Douglas, Nataki C., additional, Dowdy, Sean C., additional, Eckert, Linda O., additional, Fialkow, Michael, additional, Forman, Eric J., additional, Frumovitz, Michael, additional, Gehrig, Paola Alvarez, additional, Gershenson, David M., additional, Gilner, Jennifer Bushman, additional, Havrilesky, Laura J., additional, Hill, Cherie C., additional, Hur, Hye-Chun, additional, Jhingran, Anuja, additional, Kelley, James M., additional, Kirby, Anna C., additional, Kuller, Jeffrey A., additional, Lara-Torre, Eduardo, additional, Lentz, Gretchen M., additional, Lobo, Roger A., additional, Lu, Karen H., additional, Mendiratta, Vicki, additional, Meyer, Larissa A., additional, Miller, Jane L., additional, Nica, Andra, additional, Nunziato, Jaclyn D., additional, Orr, James W., additional, Padro, Amanda, additional, Phoolcharoen, Natacha, additional, Price, Thomas M., additional, Rackow, Beth W., additional, Ramirez, Pedro T., additional, Raymond, Licia, additional, Rhee, Eleanor H.J., additional, Rivlin, Katherine, additional, Rock, David T., additional, Ryntz, Timothy, additional, Salcedo, Mila Pontremoli, additional, Salvo, Gloria, additional, Sandadi, Samith, additional, Schmeler, Kathleen M., additional, Smith, Judith A., additional, Soliman, Pamela T., additional, Sood, Anil K., additional, Thaker, Premal H., additional, Truong, Mireille, additional, Turocy, Jenna, additional, Valea, Fidel A., additional, Watson, Catherine H., additional, Westin, Shannon N., additional, and Williams, Zev, additional

Published
2022
Full Text
View/download PDF

40. Rational combination therapy with PARP and MEK inhibitors capitalizes on therapeutic liabilities in RAS mutant cancers

Author

Sun, Chaoyang, Fang, Yong, Yin, Jun, Chen, Jian, Ju, Zhenlin, Zhang, Dong, Chen, Xiaohua, Vellano, Christopher P, Jeong, Kang Jin, Ng, Patrick Kwok-Shing, Eterovic, Agda Karina B, Bhola, Neil H, Lu, Yiling, Westin, Shannon N, Grandis, Jennifer R, Lin, Shiaw-Yih, Scott, Kenneth L, Peng, Guang, Brugge, Joan, and Mills, Gordon B

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Cancer, Rare Diseases, Orphan Drug, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cell Line, Tumor, DNA Damage, Drug Resistance, Neoplasm, Drug Synergism, Female, Forkhead Box Protein O3, Genes, ras, Homologous Recombination, MAP Kinase Signaling System, Mice, Mitogen-Activated Protein Kinase Kinases, Mutation, Neoplasms, Ovarian Neoplasms, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases, Protein Kinase Inhibitors, Xenograft Model Antitumor Assays, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Mutant RAS has remained recalcitrant to targeted therapy efforts. We demonstrate that combined treatment with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors and mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors evokes unanticipated, synergistic cytotoxic effects in vitro and in vivo in multiple RAS mutant tumor models across tumor lineages where RAS mutations are prevalent. The effects of PARP and MEK inhibitor combinations are independent of BRCA1/2 and p53 mutation status, suggesting that the synergistic activity is likely to be generalizable. Synergistic activity of PARP and MEK inhibitor combinations in RAS mutant tumors is associated with (i) induction of BIM-mediated apoptosis, (ii) decrease in expression of components of the homologous recombination DNA repair pathway, (iii) decrease in homologous recombination DNA damage repair capacity, (iv) decrease in DNA damage checkpoint activity, (v) increase in PARP inhibitor-induced DNA damage, (vi) decrease in vascularity that could increase PARP inhibitor efficacy by inducing hypoxia, and (vii) elevated PARP1 protein, which increases trapping activity of PARP inhibitors. Mechanistically, enforced expression of FOXO3a, which is a target of the RAS/MAPK pathway, was sufficient to recapitulate the functional consequences of MEK inhibitors including synergy with PARP inhibitors. Thus, the ability of mutant RAS to suppress FOXO3a and its reversal by MEK inhibitors accounts, at least in part, for the synergy of PARP and MEK inhibitors in RAS mutant tumors. The rational combination of PARP and MEK inhibitors warrants clinical investigation in patients with RAS mutant tumors where there are few effective therapeutic options.

Published
2017

41. Clinical significance of homologous recombination deficiency score testing in endometrial Cancer

Author

Siedel, Jean H., Ring, Kari L., Hu, Wei, Dood, Robert L., Wang, Ying, Baggerly, Keith, Darcy, Kathleen M., Conrads, Thomas P., Gallagher, Shannon, Tshiaba, Placede, Neff, Chris, Timms, Kirsten M., Mangala, Selanere, Westin, Shannon N., Broaddus, Russell, Lopez-Berestein, Gabriel, Lu, Karen H., Coleman, Robert L., Maxwell, George L., and Sood, Anil K.

Published
2021
Full Text
View/download PDF

45. Author Correction: Androgen receptor blockade promotes response to BRAF/MEK-targeted therapy

Author

Vellano, Christopher P., White, Michael G., Andrews, Miles C., Chelvanambi, Manoj, Witt, Russell G., Daniele, Joseph R., Titus, Mark, McQuade, Jennifer L., Conforti, Fabio, Burton, Elizabeth M., Lastrapes, Matthew J., Ologun, Gabriel, Cogdill, Alexandria P., Morad, Golnaz, Prieto, Peter, Lazar, Alexander J., Chu, Yanshuo, Han, Guangchun, Khan, M. A. Wadud, Helmink, Beth, Davies, Michael A., Amaria, Rodabe N., Kovacs, Jeffrey J., Woodman, Scott E., Patel, Sapna, Hwu, Patrick, Peoples, Michael, Lee, Jeffrey E., Cooper, Zachary A., Zhu, Haifeng, Gao, Guang, Banerjee, Hiya, Lau, Mike, Gershenwald, Jeffrey E., Lucci, Anthony, Keung, Emily Z., Ross, Merrick I., Pala, Laura, Pagan, Eleonora, Segura, Rossana Lazcano, Liu, Qian, Borthwick, Mikayla S., Lau, Eric, Yates, Melinda S., Westin, Shannon N., Wani, Khalida, Tetzlaff, Michael T., Haydu, Lauren E., Mahendra, Mikhila, Ma, XiaoYan, Logothetis, Christopher, Kulstad, Zachary, Johnson, Sarah, Hudgens, Courtney W., Feng, Ningping, Federico, Lorenzo, Long, Georgina V., Futreal, P. Andrew, Arur, Swathi, Tawbi, Hussein A., Moran, Amy E., Wang, Linghua, Heffernan, Timothy P., Marszalek, Joseph R., and Wargo, Jennifer A.

Published
2023
Full Text
View/download PDF

48. Molecular Analysis of Clinically Defined Subsets of High-Grade Serous Ovarian Cancer

Author

Lee, Sanghoon, Zhao, Li, Rojas, Christine, Bateman, Nicholas W., Yao, Hui, Lara, Olivia D., Celestino, Joseph, Morgan, Margaret B., Nguyen, Tri V., Conrads, Kelly A., Rangel, Kelly M., Dood, Robert L., Hajek, Richard A., Fawcett, Gloria L., Chu, Randy A., Wilson, Katlin, Loffredo, Jeremy L., Viollet, Coralie, Jazaeri, Amir A., Dalgard, Clifton L., Mao, Xizeng, Song, Xingzhi, Zhou, Ming, Hood, Brian L., Banskota, Nirad, Wilkerson, Matthew D., Te, Jerez, Soltis, Anthony R., Roman, Kristin, Dunn, Andrew, Cordover, David, Eterovic, Agda Karina, Liu, Jinsong, Burks, Jared K., Baggerly, Keith A., Fleming, Nicole D., Lu, Karen H., Westin, Shannon N., Coleman, Robert L., Mills, Gordon B., Casablanca, Yovanni, Zhang, Jianhua, Conrads, Thomas P., Maxwell, George L., Futreal, P. Andrew, and Sood, Anil K.

Published
2020
Full Text
View/download PDF

50. Abstract A077: The utility of surgical minimal residual disease after frontline treatment for prognostic and investigational opportunities in advanced ovarian cancer

Author

Knisely, Anne, primary, Nitecki, Roni, additional, Rauh-Hain, J. Alejandro, additional, Hillman, R. Tyler, additional, Taylor, Jolyn S., additional, Ramondetta, Lois M., additional, Grinsfelder, Michaela O., additional, Cobb, Lauren P., additional, Boruta, David M., additional, Richardson, Gwyn, additional, Soliman, Pamela T., additional, Shafer, Aaron, additional, Westin, Shannon N., additional, Fleming, Nicole D., additional, Sims, Travis T., additional, Sood, Anil K., additional, Ramirez, Pedro T., additional, Lu, Karen H., additional, and Jazaeri, Amir A., additional

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results