Dear Colleagues,

In 1865, the French physician Armand Trousseau described the association between gastrointestinal cancer and superficial migratory thrombophlebitis. Trousseau himself succumbed to gastric or pancreatic cancer after he noticed an inflamed and thrombosed vein, nowadays referred to as the "Trousseau’s sign of malignancy." More than 150 years later, gastric and pancreatic cancer are still considered the most thrombogenic tumor entities, and tissue factor (TF) has been identified as a key player mediating paraneoplastic coagulation activation.

TF is a transmembrane glycoprotein that functions as the cellular receptor and cofactor for the coagulation serine protease, factor VIIa (FVIIa). TF is constitutively expressed by many cancer cells and may also be induced in non-transformed cells of the tumor microenvironment under inflammatory or hypoxic conditions. Over the last few decades, tremendous progress has been made in our understanding of how TF promotes not only thrombin generation and fibrin formation, the key events underlying cancer-associated thrombosis (CAT), but also primary tumor growth and hematogenous metastasis. Pro-inflammatory and pro-angiogenic cell signaling by TF/FVIIa and TF/FVIIa/FXa complexes through cleavage activation of protease-activated receptors (PARs) as well as downstream generation of coagulation proteases such as thrombin represent promising targets for both anti-cancer therapy and CAT management. Moreover, circulating TF has emerged as a potential diagnostic, prognostic and predictive biomarker in solid cancers and hematological malignancies.

This Special Issue of Cancers focuses on the intriguing roles of TF and downstream coagulation proteases in tumor biology and paraneoplastic clotting abnormalities, thus setting the base for future experimental and clinical research investigating the detrimental bidirectional relationships between cancer, inflammation and thrombosis.

Prof. Dr. Florian Langer
Guest Editor

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• PAR signaling 
• Angiogenesis 
• Hematogenous Metastasis 
• Venous thromboembolism 
• Disseminated intravascular coagulation 
• Prediction of CAT