Differential platelet levels affect response to taxane-based therapy in ovarian cancer

Justin Bottsford-Miller; Hyun-Jin Choi; Heather J Dalton; Rebecca L Stone; Min Soon Cho; Monika Haemmerle; Alpa M Nick; Sunila Pradeep; Behrouz Zand; Rebecca A Previs; Chad V Pecot; Erin King Crane; Wei Hu; Susan K Lutgendorf; Vahid Afshar-Kharghan; Anil K Sood

doi:10.1158/1078-0432.ccr-14-0870

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Differential platelet levels affect response to taxane-based therapy in ovarian cancer

Journal article

Open access

Peer reviewed

Differential platelet levels affect response to taxane-based therapy in ovarian cancer

Justin Bottsford-Miller, Hyun-Jin Choi, Heather J Dalton, Rebecca L Stone, Min Soon Cho, Monika Haemmerle, Alpa M Nick, Sunila Pradeep, Behrouz Zand, Rebecca A Previs, …

Clinical cancer research, Vol.21(3), pp.602-610

02/01/2015

DOI: 10.1158/1078-0432.ccr-14-0870

PMCID: PMC4315757

PMID: 25473001

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Abstract

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. 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. 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. Platelet-driven effects of chemotherapy response may explain clinical observations.

Biomarkers

Humans

Middle Aged

Ovarian Neoplasms - pathology

Drug Resistance, Neoplasm

Ovarian Neoplasms - complications

Aged, 80 and over

Adult

Female

Retrospective Studies

Ovarian Neoplasms - drug therapy

Disease Models, Animal

Neoplasm Recurrence, Local

Ovarian Neoplasms - blood

Treatment Outcome

Tumor Burden

Disease Progression

Xenograft Model Antitumor Assays

Taxoids - administration & dosage

Animals

Platelet Count

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Thrombosis - etiology

Cell Line, Tumor

Aged

Bridged-Ring Compounds - administration & dosage

Details

Title: Subtitle: Differential platelet levels affect response to taxane-based therapy in ovarian cancer
Creators: Justin Bottsford-Miller - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Hyun-Jin Choi - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Heather J Dalton - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Rebecca L Stone - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Min Soon Cho - Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Monika Haemmerle - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Alpa M Nick - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Sunila Pradeep - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Behrouz Zand - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Rebecca A Previs - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Chad V Pecot - Department of Molecular Therapeutics, University of North Carolina Lineberger Comprehensive Cancer Center
Erin King Crane - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Wei Hu - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Susan K Lutgendorf - Department of Psychology, Obstetrics and Gynecology, and Urology, University of Iowa, Iowa City, Iowa
Vahid Afshar-Kharghan - Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Anil K Sood - 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
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.21(3), pp.602-610
DOI: 10.1158/1078-0432.ccr-14-0870
PMID: 25473001
PMCID: PMC4315757
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: United States
Grant note: UH2 TR000943 / NCATS NIH HHS T32 CA101642 / NCI NIH HHS CA177909 / NCI NIH HHS R01 CA177909 / NCI NIH HHS P50CA083639 / NCI NIH HHS CA016672 / NCI NIH HHS P50 CA098258 / NCI NIH HHS #CA016672 / NCI NIH HHS R01 CA109298 / NCI NIH HHS U54 CA096300 / NCI NIH HHS CA109298 / NCI NIH HHS UH2TR000943 / NCATS NIH HHS R01 CA140933 / NCI NIH HHS P30 CA016672 / NCI NIH HHS U54CA151668 / NCI NIH HHS U54 CA151668 / NCI NIH HHS P50 CA083639 / NCI NIH HHS P50CA098258 / NCI NIH HHS U54 CA096297 / NCI NIH HHS U54CA96297 / NCI NIH HHS U54CA96300 / NCI NIH HHS CA101642 / NCI NIH HHS
Language: English
Date published: 02/01/2015
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Obstetrics and Gynecology; Urology
Record Identifier: 9984002315902771

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