PCI-27483 - Targets: Cancer & Thrombosis
Factor VII Close
Factor VIICoagulation Factors V, VII, X and II are substances in blood essential to the normal clotting process.is a blood protein involved in clotting. Many types of cancer, such as lung, breast, pancreatic, colorectal, gastric and others, express high levels of a cell surface protein known as Tissue Factor. CloseTissue FactorThis factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. After binding to Tissue Factor, Factor VII becomes activated and triggers a host of pathologic processes in the tumor microenvironment that facilitate the growth, invasion and spread of many cancers. Activation of Factor VII (Factor VIIa) by Tissue Factor also leads to the high incidence of thromboembolic ClosethromboembolicFormation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel. The clot may plug a vessel in the lungs (pulmonary embolism), brain (stroke), gastrointestinal tract, kidneys, or leg. Thromboembolism is an important cause of morbidity (disease) and mortality (death), especially in adults. Treatment may involve anticoagulants (bloodthinners), aspirin, or vasodilators (drugs that relax and widen vessels). complications seen in cancer patients.
Factor VIIa contributes to:
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Role in cancer:
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PCI-27483 is a novel first-in-class small molecule inhibitor, which selectively targets the Factor VIIa/TF complex. Inhibitors of this complex may reduce tumor growth and metastases and may reduce the incidence of venous thromboembolism. ClosethromboembolismFormation in a blood vessel of a clot (thrombus) that breaks loose and is carried by the blood stream to plug another vessel. The clot may plug a vessel in the lungs (pulmonary embolism), brain (stroke), gastrointestinal tract, kidneys, or leg. Thromboembolism is an important cause of morbidity (disease) and mortality (death), especially in adults. Treatment may involve anticoagulants (bloodthinners), aspirin, or vasodilators (drugs that relax and widen vessels). Thromboembolic complications are a leading cause of death in patients with cancer and anticoagulant treatment has been shown to improve survival in a variety of cancers. (Ref 1.)
Animation of PCI-27483 on Cell Signaling
Pancreatic Cancer
- 4th leading cause of cancer death in the USA
- Pancreatic cancer is a malignant tumor of the pancreas. Approximately 90% of pancreatic cancers express Tissue Factor (TF).
- Each year 230,000 individuals worldwide are diagnosed with this condition. In the U.S. more than 34,000 are diagnosed each year. Depending on the extent of the tumor at the time of diagnosis, the prognosis is generally regarded as poor, with less than 3% of those diagnosed surviving five years after diagnosis. Median survival with metastatic pancreatic cancer is 5.7 to 6.4 months.
News
- IND opened August, 2008.
- Completion of Phase I clinical trial of Factor VIIa Inhibitor in November, 2008.
- Preparing the initiation of a Phase Ib/II trial that will evaluate PCI-27483’s effect in pancreatic cancer patients.
The Science behind PCI-27483
- View a Pharmacyclics authored poster presentation on the FVIIa Inhibitor from the American Association for Cancer Research 2008 annual meeting. The poster presents the results of research where PCI-27483 was applied in a pancreatic tumor xenograft model.
- NCI sponsoring clinical trials with anticoagulant as adjunct therapy in pancreatic cancer
Ref 1.: Journal of Clinical Oncology : Vol 23 . Number 10 . April 1, 2005 The Effect of Low Molecular Weight Heparin on Survival in Patients with Advanced Malignancy : Clara P.W. Klerk, Susanne M. Smorenburg, Hans-Martin Otten, Anthonie W.A.Lensing, martin H. Prins, Franco Piovella, Paolo Prandoni, Monique M.E.M. Bos, Dick j. Richel , Geertjan van Tienhoven, and Harry Buller