Ines Lohse1,2,3, Diana J Azzam1,2,3, Hassan Al-Ali4,5,6,7, Claude-Henry Volmar1,2,3, Shaun P Brothers1,2,3, Tan A Ince4,8, Claes Wahlestedt9,2. 1. Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 2. Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 3. Molecular Therapeutics Shared Resource, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, U.S.A. 4. Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, U.S.A. 5. Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 6. Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 7. Peggy and Harold Katz Drug Discovery Center, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 8. Department of Pathology and Interdisciplinary Stem Cell Institute, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. 9. Center for Therapeutic Innovation, Miller School of Medicine, University of Miami, Miami, FL, U.S.A. cwahlestedt@med.miami.edu.
Abstract
BACKGROUND: Treatment options for patients with platinum-resistant ovarian cancer are generally palliative in nature and rarely have realistic potential to be curative. Because many patients with recurrent ovarian cancer receive aggressive chemotherapy for prolonged periods, sometimes continuously, therapy-related toxicities are a major factor in treatment decisions. The use of ex vivo drug sensitivity screens has the potential to improve the treatment of patients with platinum-resistant ovarian cancer by providing personalized treatment plans and thus reducing toxicity from unproductive therapy attempts. MATERIALS AND METHODS: We evaluated the treatment responses of a set of six early-passage patient-derived ovarian cancer cell lines towards a set of 30 Food and Drug Administration-approved chemotherapy drugs using drug-sensitivity testing. RESULTS: We observed a wide range of treatment responses of the cell lines. While most compounds displayed vastly different treatment responses between cell lines, we found that some compounds such as docetaxel and cephalomannine reduced cell survival of all cell lines. CONCLUSION: We propose that ex vivo drug-sensitivity screening holds the potential to greatly improve patient outcomes, especially in a population where multiple continuous treatments are not an option due to advanced disease, rapid disease progression, age or poor overall health. This approach may also be useful to identify potential novel therapeutics for patients with ovarian cancer. Copyright
BACKGROUND: Treatment options for patients with platinum-resistant ovarian cancer are generally palliative in nature and rarely have realistic potential to be curative. Because many patients with recurrent ovarian cancer receive aggressive chemotherapy for prolonged periods, sometimes continuously, therapy-related toxicities are a major factor in treatment decisions. The use of ex vivo drug sensitivity screens has the potential to improve the treatment of patients with platinum-resistant ovarian cancer by providing personalized treatment plans and thus reducing toxicity from unproductive therapy attempts. MATERIALS AND METHODS: We evaluated the treatment responses of a set of six early-passage patient-derived ovarian cancer cell lines towards a set of 30 Food and Drug Administration-approved chemotherapy drugs using drug-sensitivity testing. RESULTS: We observed a wide range of treatment responses of the cell lines. While most compounds displayed vastly different treatment responses between cell lines, we found that some compounds such as docetaxel and cephalomannine reduced cell survival of all cell lines. CONCLUSION: We propose that ex vivo drug-sensitivity screening holds the potential to greatly improve patient outcomes, especially in a population where multiple continuous treatments are not an option due to advanced disease, rapid disease progression, age or poor overall health. This approach may also be useful to identify potential novel therapeutics for patients with ovarian cancer. Copyright
Authors: Ronan T Swords; Diana Azzam; Hassan Al-Ali; Ines Lohse; Claude-Henry Volmar; Justin M Watts; Aymee Perez; Ana Rodriguez; Fernando Vargas; Roy Elias; Francisco Vega; Arthur Zelent; Shaun P Brothers; Taher Abbasi; Jonathan Trent; Shaukat Rangwala; Yehuda Deutsch; Eibhlin Conneally; Leylah Drusbosky; Christopher R Cogle; Claes Wahlestedt Journal: Leuk Res Date: 2017-11-11 Impact factor: 3.156
Authors: Tea Pemovska; Mika Kontro; Bhagwan Yadav; Henrik Edgren; Samuli Eldfors; Agnieszka Szwajda; Henrikki Almusa; Maxim M Bespalov; Pekka Ellonen; Erkki Elonen; Bjørn T Gjertsen; Riikka Karjalainen; Evgeny Kulesskiy; Sonja Lagström; Anna Lehto; Maija Lepistö; Tuija Lundán; Muntasir Mamun Majumder; Jesus M Lopez Marti; Pirkko Mattila; Astrid Murumägi; Satu Mustjoki; Aino Palva; Alun Parsons; Tero Pirttinen; Maria E Rämet; Minna Suvela; Laura Turunen; Imre Västrik; Maija Wolf; Jonathan Knowles; Tero Aittokallio; Caroline A Heckman; Kimmo Porkka; Olli Kallioniemi; Krister Wennerberg Journal: Cancer Discov Date: 2013-09-20 Impact factor: 39.397
Authors: Heikki Kuusanmäki; Olli Dufva; Elina Parri; Arjan J van Adrichem; Hanna Rajala; Muntasir M Majumder; Bhagwan Yadav; Alun Parsons; Wing C Chan; Krister Wennerberg; Satu Mustjoki; Caroline A Heckman Journal: Oncotarget Date: 2017-10-31
Authors: Melissa A Merritt; Stefan Bentink; Matthew Schwede; Marcin P Iwanicki; John Quackenbush; Terri Woo; Elin S Agoston; Ferenc Reinhardt; Christopher P Crum; Ross S Berkowitz; Samuel C Mok; Abigail E Witt; Michelle A Jones; Bin Wang; Tan A Ince Journal: PLoS One Date: 2013-11-26 Impact factor: 3.240