title: Differential platelet levels affect response to taxane-based therapy in ovarian cancer.
abstract: OBJECTIVE
  We hypothesized that platelet levels during therapy could serve as a biomarker for response to therapy and that manipulation of platelet levels could impact responsiveness to chemotherapy.
  
  
  METHODS
  The medical records of patients with recurrent or progressive ovarian cancer were retrospectively queried for changes in platelet and CA-125 levels during primary therapy. In vitro coculture experiments and in vivo orthotopic models of human ovarian cancer in mice were used to test the effect of modulating platelet levels on tumor growth and responsiveness to docetaxel.
  
  
  RESULTS
  Thrombocytosis at the diagnosis of ovarian cancer was correlated with decreased interval to progression (P = 0.05) and median overall survival (P = 0.007). Mean platelet levels corrected during primary therapy and rose at recurrence. Contrary to treatment-responsive patients, in a cohort of patients refractory to primary therapy, platelet levels did not normalize during therapy. In A2780, HeyA8, and SKOV3-ip1 ovarian cancer cell lines, platelet coculture protected against apoptosis (P < 0.05). In orthotopic models of human ovarian cancer, platelet depletion resulted in 70% reduced mean tumor weight (P < 0.05). Compared with mice treated with docetaxel, mice treated with both docetaxel and platelet-depleting antibody had a 62% decrease in mean tumor weight (P = 0.04). Platelet transfusion increased mean aggregate tumor weight 2.4-fold (P < 0.05), blocked the effect of docetaxel on tumor growth (P = 0.55) and decreased tumor cell apoptosis. Pretransfusion aspirinization of the platelets blocked the growth-promoting effects of transfusion.
  
  
  CONCLUSIONS
  Platelet-driven effects of chemotherapy response may explain clinical observations.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Justin
authors.initials: J
authors.lastname: Bottsford-Miller
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.affiliation: Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Min Soon
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Monika
authors.initials: M
authors.lastname: Haemmerle
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sunila
authors.initials: S
authors.lastname: Pradeep
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zand
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Previs
authors.affiliation: Department of Molecular Therapeutics, University of North Carolina Lineberger Comprehensive Cancer Center.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Erin King
authors.initials: EK
authors.lastname: Crane
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Psychology, Obstetrics and Gynecology, and Urology, University of Iowa, Iowa City, Iowa.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Lutgendorf
authors.affiliation: Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Vahid
authors.initials: V
authors.lastname: Afshar-Kharghan
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, Texas. asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010976:Platelet Count; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D013927:Thrombosis / Q000209:etiology; D016896:Treatment Outcome; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane