TY - JOUR

T1 - Pleiotropic Effects of Heparins

T2 - From Clinical Applications to Molecular Mechanisms in Hepatocellular Carcinoma

AU - Korhan, Peyda

AU - Yılmaz, Yeliz

AU - Bağırsakçı, Ezgi

AU - Güneş, Ayşim

AU - Topel, Hande

AU - Carr, Brian I

AU - Atabey, Neşe

PY - 2018

Y1 - 2018

N2 - Hepatocellular carcinoma (HCC) is a major health problem worldwide and most cases are incurable because of late presentation. It is the most common primary neoplasm of the liver and often arises in the context of a chronic liver disease that impairs coagulation. Portal vein thrombosis (PVT) is a common complication of HCC that is associated with a poor prognosis. Heparin derivatives are widely used in the management of venous thromboembolism (VTE). Among them low molecular weight heparin (LMWH) favorably influences the survival in patients with advanced cancer, including HCC. Due to their pleiotropic function, heparins affect tumorigenesis in many ways and may promote or hamper tumorigenic transformation depending on the cancer type and cancer stage along with their structural properties and concentration. Thus, their application as an antithrombotic along with the conventional therapy regime should be carefully planned to develop the best management strategies. In this review, we first will briefly review clinical applications of heparin derivatives in the management of cancer with a particular focus on HCC. We then summarize the state of knowledge whereby heparin can crosstalk with molecules playing a role in hepatocarcinogenesis. Lastly, we highlight new experimental and clinical research conducted with the aim of moving towards personalized therapy in cancer patients at risk of thromboembolism.

AB - Hepatocellular carcinoma (HCC) is a major health problem worldwide and most cases are incurable because of late presentation. It is the most common primary neoplasm of the liver and often arises in the context of a chronic liver disease that impairs coagulation. Portal vein thrombosis (PVT) is a common complication of HCC that is associated with a poor prognosis. Heparin derivatives are widely used in the management of venous thromboembolism (VTE). Among them low molecular weight heparin (LMWH) favorably influences the survival in patients with advanced cancer, including HCC. Due to their pleiotropic function, heparins affect tumorigenesis in many ways and may promote or hamper tumorigenic transformation depending on the cancer type and cancer stage along with their structural properties and concentration. Thus, their application as an antithrombotic along with the conventional therapy regime should be carefully planned to develop the best management strategies. In this review, we first will briefly review clinical applications of heparin derivatives in the management of cancer with a particular focus on HCC. We then summarize the state of knowledge whereby heparin can crosstalk with molecules playing a role in hepatocarcinogenesis. Lastly, we highlight new experimental and clinical research conducted with the aim of moving towards personalized therapy in cancer patients at risk of thromboembolism.

KW - Anticoagulants/pharmacology

KW - Carcinogenesis/drug effects

KW - Carcinoma, Hepatocellular/complications

KW - Genetic Pleiotropy/drug effects

KW - Heparin/pharmacology

KW - Humans

KW - Liver Neoplasms/complications

KW - Venous Thromboembolism/drug therapy

U2 - 10.1155/2018/7568742

DO - 10.1155/2018/7568742

M3 - Review

C2 - 30425976

VL - 2018

SP - 7568742

JO - Canadian Journal of Gastroenterology

JF - Canadian Journal of Gastroenterology

SN - 2291-2789

ER -