Acute coronary syndromes, ACS, percutaneous coronary intervention, PCI, clopidogrel, prasugrel, CYP2C19 Overview Warfarin (Coumadin) is the most commonly used vitamin K antagonist. It has demonstrated effectiveness for the primary and secondary prevention of venous thromboembolism, for the prevention of systemic embolism in patients with prosthetic heart valves or atrial fibrillation, as an adjunct in the prophylaxis of systemic embolism after myocardial infarction, and for reducing the risk of recurrent myocardial infarction.
Clopidogrel Dosing and CYP2C19 Overview Clopidogrel (Plavix), a second-generation thienopyridine that inhibits platelet aggregation, is a mainstay, along with aspirin, in the management of patients with coronary artery disease, with acute coronary syndromes (ACS), and/or after percutaneous coronary interventions (PCI). Yet, a significant proportion of patients remains at risk for subsequent death, myocardial infarction (MI), stent thrombosis, and stroke because of insufficient clopidogrel-induced platelet inhibition.
Lung Cancer and EGFR Overview A substantial percentage of lung cancers express cell surface epidermal growth factor receptors (EGFRs). As activation of these cell surface receptors has been shown in experimental systems to result in the growth and progression of the malignancy, there have been considerable pre-clinical and clinical research efforts directed toward the development of effective inhibitors of the EGFR.
Fluorouracil Toxicity and DPYD Overview 5-Fluorouracil (5FU) is a fluorinated pyrimidine analogue commonly used in combination chemotherapy regimens for patients with breast, colorectal, lung, and other malignancies. Dihydropyrimidine dehydrogenase (DPD), an enzyme encoded by the DPYD gene, is the rate-limiting step in pyrimidine catabolism and deactivates more than 80% of standard doses of 5FU and the oral 5FU prodrug capecitabine.
Colorectal Cancer and KRAS Overview One actively investigated approach in the management of advanced and metastatic colorectal cancer (CRC) has been the delivery of agents whose primary purpose is to interfere with the biological activity of the epidermal growth factor receptor (EGFR). However, it is well-recognized that only a subset of patients whose colorectal tumors have been demonstrated to overexpress the EGFR receptor on their cell surfaces will actually exhibit a favorable biological and clinical response to anti-EGFR antibody therapy….
Chronic Myeloid Leukemia and BCR-ABL Overview Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is one of the few cancers that is known to caused by a single, specific genetic mutation in more than 90% of cases. The transformation to CML is caused by a reciprocal translocation of the BCR gene on chromosome 22 (at 22q11) and the ABL gene on chromosome 9 (at 9q34), resulting in a fused BCR-ABL gene dubbed the “Philadelphia chromosome.” The protein that…
Breast Cancer and HER2 Overview Approximately 30% of malignant breast cancers demonstrate overamplification of the human epidermal receptor type 2 (HER2) gene, resulting in an overexpression of the HER2 receptor, a transmembrane tyrosine kinase receptor within the epidermal growth factor receptor (EGFR) family. Activation of this class of cellular receptors is known to result in increased activity of a variety of molecular pathways associated with tumor growth and progression. Extensive published pre-clinical and clinical data have demonstrated that patients whose…