Abstract
The development of targeted therapy drugs acting on tumor growth and progression is greatly expanding these last years. Among them kinase inhibitors have a prominent position and have demonstrated efficacy and clinical benefits in solid and hematologic malignancies. Compared to conventional systemic cytotoxic chemotherapeutic agents, their specific mechanism of action limits the occurrence of adverse events. However, as targeted kinases are shared by normal cells, their inhibition can affect physiological cell function. In this review we will focus on the side effects of kinase inhibitors on blood platelets which actively use kinase-related signalling pathways to prevent haemorrhages following vessel injury. Major functions of platelets are to adhere to the subendothelial matrix and to aggregate to form a haemostatic plug preventing excessive blood loss upon vascular lesion. Several kinase inhibitors including dasatinib and ibrutinib have been reported to affect specific steps of platelet activation process and to increase bleeding risk. This has important clinical implications particularly in patients treated with antithrombotic drugs. We will describe the effect of kinase inhibitors known to affect platelet activation and discuss the potential impact of those under development that may also interfere with platelet functions.
Keywords: Targeted drugs, anticancer therapies, kinase inhibitors, platelet functions, haemostasis-related adverse events.
Current Pharmaceutical Design
Title:Targeting Kinases in Cancer Therapies: Adverse Effects on Blood Platelets
Volume: 22 Issue: 16
Author(s): Marie Levade, Sonia Severin, Marie-Pierre Gratacap, Loïc Ysebaert and Bernard Payrastre
Affiliation:
Keywords: Targeted drugs, anticancer therapies, kinase inhibitors, platelet functions, haemostasis-related adverse events.
Abstract: The development of targeted therapy drugs acting on tumor growth and progression is greatly expanding these last years. Among them kinase inhibitors have a prominent position and have demonstrated efficacy and clinical benefits in solid and hematologic malignancies. Compared to conventional systemic cytotoxic chemotherapeutic agents, their specific mechanism of action limits the occurrence of adverse events. However, as targeted kinases are shared by normal cells, their inhibition can affect physiological cell function. In this review we will focus on the side effects of kinase inhibitors on blood platelets which actively use kinase-related signalling pathways to prevent haemorrhages following vessel injury. Major functions of platelets are to adhere to the subendothelial matrix and to aggregate to form a haemostatic plug preventing excessive blood loss upon vascular lesion. Several kinase inhibitors including dasatinib and ibrutinib have been reported to affect specific steps of platelet activation process and to increase bleeding risk. This has important clinical implications particularly in patients treated with antithrombotic drugs. We will describe the effect of kinase inhibitors known to affect platelet activation and discuss the potential impact of those under development that may also interfere with platelet functions.
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Cite this article as:
Levade Marie, Severin Sonia, Gratacap Marie-Pierre, Ysebaert Loïc and Payrastre Bernard, Targeting Kinases in Cancer Therapies: Adverse Effects on Blood Platelets, Current Pharmaceutical Design 2016; 22 (16) . https://dx.doi.org/10.2174/1381612822666160226132630
DOI https://dx.doi.org/10.2174/1381612822666160226132630 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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