Kentaro Igarashi1,2,3, Kei Kawaguchi1,2, Tasuku Kiyuna1,2, Kentaro Miyake1,2, Takashi Higuchi1,2,3, Norio Yamamoto3, Katsuhiro Hayashi3, Hiroaki Kimura3, Shinji Miwa3, Shree Ram Singh4, Hiroyuki Tsuchiya5, Robert M Hoffman6,2. 1. AntiCancer, Inc., San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan. 4. Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov. 5. Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov. 6. AntiCancer, Inc., San Diego, CA, U.S.A. all@anticancer.com tsuchi@med.kanazawa-u.ac.jp singhshr@mail.nih.gov.
Abstract
BACKGROUND/AIM: Dedifferentiated liposarcoma (DDLPS) is recalcitrant type of sarcoma. DDLPS has a low survival rate with high recurrence and metastasis. In the present study, we evaluated the efficacy of several drugs against doxorubicin-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) model for precision oncology. To establish the PDOX model, a tumor from a patient who had recurrent high-grade DDLPS from the retroperitoneum was previously grown orthotopically in the retroperitoneum of nude mice. MATERIALS AND METHODS: We randomized DDLPS PDOX models into 8 treatment groups when tumor volume became approximately 100 mm3: control, no treatment; G2, doxorubicin (DOX); G3, pazopanib (PAZ); G4, gemcitabine (GEM) combined with docetaxel (DOC); G5, trabectedin (YON); G6, temozolomide (TEM); G7, palbociclib (PAL); G8, eribulin (ERB). Tumor length and width were measured both at the beginning and at the end of treatment. RESULTS: At the end of treatment (day 14), all treatments significantly inhibited DDLPS PDOX tumor growth compared to the untreated control, except DOX. ERB was significantly more effective and regressed tumor volume compared to other treatments on day 14 after initiation of treatment. No significant differences were found in the relative body weight on day 14 compared to day 0 in any group. CONCLUSION: The clinical potential of ERB against DDLPS is herein presented in a PDOX model. Copyright
BACKGROUND/AIM: Dedifferentiated liposarcoma (DDLPS) is recalcitrant type of sarcoma. DDLPS has a low survival rate with high recurrence and metastasis. In the present study, we evaluated the efficacy of several drugs against doxorubicin-resistant DDLPS in a patient-derived orthotopic xenograft (PDOX) model for precision oncology. To establish the PDOX model, a tumor from a patient who had recurrent high-grade DDLPS from the retroperitoneum was previously grown orthotopically in the retroperitoneum of nude mice. MATERIALS AND METHODS: We randomized DDLPS PDOX models into 8 treatment groups when tumor volume became approximately 100 mm3: control, no treatment; G2, doxorubicin (DOX); G3, pazopanib (PAZ); G4, gemcitabine (GEM) combined with docetaxel (DOC); G5, trabectedin (YON); G6, temozolomide (TEM); G7, palbociclib (PAL); G8, eribulin (ERB). Tumor length and width were measured both at the beginning and at the end of treatment. RESULTS: At the end of treatment (day 14), all treatments significantly inhibited DDLPS PDOX tumor growth compared to the untreated control, except DOX. ERB was significantly more effective and regressed tumor volume compared to other treatments on day 14 after initiation of treatment. No significant differences were found in the relative body weight on day 14 compared to day 0 in any group. CONCLUSION: The clinical potential of ERB against DDLPS is herein presented in a PDOX model. Copyright
Authors: P J Houghton; C F Stewart; P J Cheshire; L B Richmond; M N Kirstein; C A Poquette; M Tan; H S Friedman; T P Brent Journal: Clin Cancer Res Date: 2000-10 Impact factor: 12.531
Authors: Kei Kawaguchi; Kentaro Igarashi; Kentaro Miyake; Tasuku Kiyuna; Masuyo Miyake; Arun S Singh; Bartosz Chmielowski; Scott D Nelson; Tara A Russell; Sarah M Dry; Yunfeng Li; Michiaki Unno; Shree Ram Singh; Fritz C Eilber; Robert M Hoffman Journal: J Drug Target Date: 2018-08-23 Impact factor: 5.121
Authors: W K Yung; M D Prados; R Yaya-Tur; S S Rosenfeld; M Brada; H S Friedman; R Albright; J Olson; S M Chang; A M O'Neill; A H Friedman; J Bruner; N Yue; M Dugan; S Zaknoen; V A Levin Journal: J Clin Oncol Date: 1999-09 Impact factor: 44.544
Authors: Takashi Murakami; Jonathan DeLong; Fritz C Eilber; Ming Zhao; Yong Zhang; Nan Zhang; Arun Singh; Tara Russell; Samantha Deng; Jose Reynoso; Cuong Quan; Yukihiko Hiroshima; Ryusei Matsuyama; Takashi Chishima; Kuniya Tanaka; Michael Bouvet; Sant Chawla; Itaru Endo; Robert M Hoffman Journal: Oncotarget Date: 2016-03-15
Authors: Takashi Murakami; Arun S Singh; Tasuku Kiyuna; Sarah M Dry; Yunfeng Li; Aaron W James; Kentaro Igarashi; Kei Kawaguchi; Jonathan C DeLong; Yong Zhang; Yukihiko Hiroshima; Tara Russell; Mark A Eckardt; Jane Yanagawa; Noah Federman; Ryusei Matsuyama; Takashi Chishima; Kuniya Tanaka; Michael Bouvet; Itaru Endo; Fritz C Eilber; Robert M Hoffman Journal: Oncotarget Date: 2016-07-26