Author + information
- Joy R. Wright, PhDa,∗,
- Meera Chauhan, PhDa,b,∗,
- Chirag Shah, PhDa,
- Alistair Ring, MDc,
- Anne L. Thomas, PhDb,
- Alison H. Goodall, PhDa,b,† and
- David Adlam, DPhila,∗,† (, )@LeicesterBRC@UoLCVS
- aDepartment of Cardiovascular Sciences, University of Leicester, and the National Institutes of Health Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, United Kingdom
- bLeicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom
- cDepartment of Medicine, Royal Marsden Hospital NHS Trust, London, United Kingdom
- ↵∗Address for correspondence:
Dr. David Adlam, Department of Cardiovascular Sciences, Glenfield Hospital, Groby Road, Leicester LE3 9QP, United Kingdom.
Background In cancer, platelets may facilitate metastatic spread by a number of mechanisms as well as contribute to thrombotic complications. Ticagrelor, a platelet antagonist- that blocks adenosine diphosphate activation of platelet P2Y12 receptors, is widely used in the treatment of cardiovascular disease, but its efficacy in cancer remains unknown.
Objectives This study sought to evaluate the effect of aspirin and ticagrelor monotherapy, as well as dual antiplatelet therapy, on platelet activation in cancer.
Methods This study consisted of 2 phases: first, an in vitro study of human platelet−tumor cell interaction; and second, a randomized crossover clinical trial of 22 healthy donors and 16 patients with metastatic breast or colorectal cancer. Platelet activation and inhibition were measured by aggregometry and flow cytometry.
Results In vitro, tumor cells induced cellular clusters that were predominantly platelet−platelet aggregates. Ticagrelor significantly inhibited formation of large tumor cell-induced platelet−platelet aggregates: 65.4 ± 4.8% to 50.9 ± 5.9% (p = 0.002) and 62.3 ± 3.1% to 48.3 ± 7.3% (p = 0.014) for MCF-7 and HT-29-induced aggregation, respectively. Supporting this finding, cancer patients on ticagrelor had significantly reduced levels of spontaneous platelet aggregation and activation compared with baseline; 14.8 ± 2.7% at baseline to 7.8 ± 2.3% with ticagrelor (p = 0.012).
Conclusions Our findings suggested that P2Y12 inhibition with ticagrelor might reduce spontaneous platelet aggregation and activation in patients with metastatic cancer and merits further investigation in patients at high risk of cancer-associated thrombosis. (Ticagrelor-Oncology [TICONC] Study; EudraCT: 2014-004049-29)
↵∗ Drs. Wright and Chauhan contributed equally to this work and are joint first authors.
↵† Drs. Goodall and Adlam contributed equally to this work and are joint senior authors.
This study was supported by an investigator-sponsored study grant from AstraZeneca (No. ISSBRIL0264). Dr. Thomas has received conference attendance support from Bristol-Myers Squibb; and has been a member of the Speakers Bureau for Amgen. Dr. Adlam has received funding from Abbott Vascular to support a clinical research fellow conducting unrelated research; has received in-kind support from AstraZeneca for unrelated research in addition to the funding specified for this study; and has undertaken consultancy with General Electric to support general research funds. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. This study was presented in part as a poster at the ESMO International Congress, September 27 to October 2, 2019, Barcelona, Spain.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: CardioOncology author instructions page.
- Received December 17, 2019.
- Revision received April 20, 2020.
- Accepted April 24, 2020.
- 2020 The Authors