ix
Preface
Dear Colleagues, This volume contains the proceedings of the Seventh “International Conference on Thrombosis and Hemostasis Issues in Cancer”, held in Bergamo, Italy, May 9-11, 2014. As attendees of previous meetings know, this conference focuses on translational research with a strong emphasis on the application of basic science concepts to solving clinical problems in patients with cancer. We present the latest (frequently unpublished) data from our colleagues, who study the pathophysiology and the prevention and treatment of thrombosis and bleeding in cancer. The setting of this meeting gives the opportunity to utilize this information in the design of new strategies for cancer treatment. This relatively “small” and intimate meeting is by now a well-known location (“the Bergamo Conference”), where basic scientists and clinician-scientists can develop collaborations, participate together in the rational design of both basic and translational studies in a harmonious and convivial atmosphere. Indeed, the meeting has become a popular venue, where colleagues involved in clinical research provide the latest findings from large clinical trials and we can assess the progress that has been made since the last time we met 2 years ago. Many observations are presented for the first time at this meeting including, for example, the critically important discovery that oncogenes directly activate blood coagulation and induce thrombosis in animal models – an update of which is the subject of the Third Simon Karpatkin Memorial Lecture given this year by Professor Janusz Rak. Included in this volume is new information on signaling pathways which are regulated by the oncogenic process. In particular, we discover the further potential for successful targeting of these pathways by inhibition of both coagulation activation and tumor growth in experimental systems. The debate on the hemostatic system imbalance associated with malignant disease continues to provide a platform for discussion. This imbalance underpins the characteristic thrombotic and hemorrhagic diatheses (e.g. the thrombohemorrhagic syndromes - THS) that commonly occur in patients with both solid tumors and hematological malignancies. Markers of coagulation activation, including procoagulant-rich microparticles (MPs) shed by tumor cells, endothelial cells, inflammatory cells and platelets, are found in excess in the circulation of patients with cancer. Along with additional biological markers, several research groups are now extending their prior exciting data using the quantification and characterization of MPs to predict venous thromboembolic events (VTE) in patients with malignancies. Large prospective studies have incorporated various biological markers into riskassessment models, which continue to be an important subject, first explored in detail at the Bergamo Meeting. Several ongoing clinical trials are now using one or more of these predictive
models to target high-risk patients for VTE prophylaxis, hopefully optimizing the risk/benefit equation. Given that activation of blood coagulation in cancer is largely oncogene-driven and indicates a more aggressive biology of tumors, it will continue to be of interest to determine if VTE prophylaxis alters the natural history of cancer – although retrospective analysis suggests that anticoagulants may affect cancer survival, the final word is not in on this complicated subject. The advent of targeted therapies in cancer has been paralleled by development of refined targeted anticoagulants that are quite efficient in prevention and treatment of VTE in the general population. It is not yet clear, however, if these new anticoagulant drugs will be as effective in the prevention and treatment of VTE in cancer patients. In view of the well-known “double-edged sword” of anti-angiogenic agents (that is, inhibiting blood vessel growth but inducing both thrombosis and bleeding), the new targeted anti-cancer drugs must be examined carefully for adverse effects on blood clotting, platelet function and fibrinolysis. Platelets, endothelial cells and fibrinolytic proteins also facilitate tumor cell interactions and locomotion. Natural anticoagulants, including heparin-like mucopolysaccharides, provide reservoirs of growth factors for tumor cells and tumorassociated heparanases may be important targets for novel approaches to cancer chemotherapy. On the basis of this new understanding of pathological thrombus formation in cancer, novel approaches to antithrombotic therapy continue to undergo development. Pre-clinical and clinical investigations on the antitumor effects of antithrombotic drugs are in progress. The success of the previous six ICTHIC conferences, which have been held nearly every other year, usually in Bergamo, Italy since 2001, together with the continued growth of information (both basic and clinical) and general interest in this important subject (thrombosis and hemorrhage in malignancy), have prompted us to convene again. The sections of this edition cover a number of different issues, including: 1. Epidemiology and risk factors for thrombosis in cancer; 2. Hypercoagulability and biomarkers for VTE in cancer; 3. Bleeding complications, microangiopathies and thrombocytopenia in cancer patients; 4. Hemostatic system and cancer progression; 5. Thrombosis in hematological disorders; 6. Thromboprophylaxis in cancer; 7. Platelets and vascular endothelium; 8. Treatment of thrombosis in cancer. We sincerely hope that this volume will serve as an up-todate review of this challenging and rapidly growing field. We thank all the authors for their contributions and wish all the participants lively discussions of these important topics.
The Conference Chairmen Anna Falanga, Benjamin Brenner, Frederick R. Rickles
Preface
Dear Colleagues, This volume contains the proceedings of the Seventh “International Conference on Thrombosis and Hemostasis Issues in Cancer”, held in Bergamo, Italy, May 9-11, 2014. As attendees of previous meetings know, this conference focuses on translational research with a strong emphasis on the application of basic science concepts to solving clinical problems in patients with cancer. We present the latest (frequently unpublished) data from our colleagues, who study the pathophysiology and the prevention and treatment of thrombosis and bleeding in cancer. The setting of this meeting gives the opportunity to utilize this information in the design of new strategies for cancer treatment. This relatively “small” and intimate meeting is by now a well-known location (“the Bergamo Conference”), where basic scientists and clinician-scientists can develop collaborations, participate together in the rational design of both basic and translational studies in a harmonious and convivial atmosphere. Indeed, the meeting has become a popular venue, where colleagues involved in clinical research provide the latest findings from large clinical trials and we can assess the progress that has been made since the last time we met 2 years ago. Many observations are presented for the first time at this meeting including, for example, the critically important discovery that oncogenes directly activate blood coagulation and induce thrombosis in animal models – an update of which is the subject of the Third Simon Karpatkin Memorial Lecture given this year by Professor Janusz Rak. Included in this volume is new information on signaling pathways which are regulated by the oncogenic process. In particular, we discover the further potential for successful targeting of these pathways by inhibition of both coagulation activation and tumor growth in experimental systems. The debate on the hemostatic system imbalance associated with malignant disease continues to provide a platform for discussion. This imbalance underpins the characteristic thrombotic and hemorrhagic diatheses (e.g. the thrombohemorrhagic syndromes - THS) that commonly occur in patients with both solid tumors and hematological malignancies. Markers of coagulation activation, including procoagulant-rich microparticles (MPs) shed by tumor cells, endothelial cells, inflammatory cells and platelets, are found in excess in the circulation of patients with cancer. Along with additional biological markers, several research groups are now extending their prior exciting data using the quantification and characterization of MPs to predict venous thromboembolic events (VTE) in patients with malignancies. Large prospective studies have incorporated various biological markers into riskassessment models, which continue to be an important subject, first explored in detail at the Bergamo Meeting. Several ongoing clinical trials are now using one or more of these predictive
models to target high-risk patients for VTE prophylaxis, hopefully optimizing the risk/benefit equation. Given that activation of blood coagulation in cancer is largely oncogene-driven and indicates a more aggressive biology of tumors, it will continue to be of interest to determine if VTE prophylaxis alters the natural history of cancer – although retrospective analysis suggests that anticoagulants may affect cancer survival, the final word is not in on this complicated subject. The advent of targeted therapies in cancer has been paralleled by development of refined targeted anticoagulants that are quite efficient in prevention and treatment of VTE in the general population. It is not yet clear, however, if these new anticoagulant drugs will be as effective in the prevention and treatment of VTE in cancer patients. In view of the well-known “double-edged sword” of anti-angiogenic agents (that is, inhibiting blood vessel growth but inducing both thrombosis and bleeding), the new targeted anti-cancer drugs must be examined carefully for adverse effects on blood clotting, platelet function and fibrinolysis. Platelets, endothelial cells and fibrinolytic proteins also facilitate tumor cell interactions and locomotion. Natural anticoagulants, including heparin-like mucopolysaccharides, provide reservoirs of growth factors for tumor cells and tumorassociated heparanases may be important targets for novel approaches to cancer chemotherapy. On the basis of this new understanding of pathological thrombus formation in cancer, novel approaches to antithrombotic therapy continue to undergo development. Pre-clinical and clinical investigations on the antitumor effects of antithrombotic drugs are in progress. The success of the previous six ICTHIC conferences, which have been held nearly every other year, usually in Bergamo, Italy since 2001, together with the continued growth of information (both basic and clinical) and general interest in this important subject (thrombosis and hemorrhage in malignancy), have prompted us to convene again. The sections of this edition cover a number of different issues, including: 1. Epidemiology and risk factors for thrombosis in cancer; 2. Hypercoagulability and biomarkers for VTE in cancer; 3. Bleeding complications, microangiopathies and thrombocytopenia in cancer patients; 4. Hemostatic system and cancer progression; 5. Thrombosis in hematological disorders; 6. Thromboprophylaxis in cancer; 7. Platelets and vascular endothelium; 8. Treatment of thrombosis in cancer. We sincerely hope that this volume will serve as an up-todate review of this challenging and rapidly growing field. We thank all the authors for their contributions and wish all the participants lively discussions of these important topics.
The Conference Chairmen Anna Falanga, Benjamin Brenner, Frederick R. Rickles
