for trial entry. Staging and treatment plans vary significantly. The panel felt BCLC staging is acceptable NVP-BEP800 for trials as long as portal vein hypertension can be measured and defined with non invasive standardized methodology and liver disease is further evaluated. Consensus in treatment must be sought to allow multinational trials and it must be recognized that first line sorafenib is not largely feasible in Asia. Finally, Asian nations must be urged to participate in clinical trials, many of which are ongoing, to advance new treatment options in this challenging disease. Introduction Receptor tyrosine kinases and protein phosphatases control reversible protein phosphorylation. This process mediates critical signaling transduction between cell and extracellular stimulation, including survival, growth and differentiation.
Dysregulation of RTK signaling pathways has been correlated with the progression of cancers with different histological origins. For example, amplification of the HER2 gene is observed BMS-599626 in 30 of breast cancer biopsies and forms the basis for the use of trastuzumab to treat breast cancer patients. The common molecular mechanisms underlying such aberrant activities are point mutation, duplication, and amplification of the RTK, which leads to gain of function and consecutive activation of the kinases in general. The fms like tyrosine kinase 3 is a class III RTK family and shares strong structural similarity with other family members including receptors for platelet derived growth factors A and B, the colony stimulating factor 1 receptor and steel factor receptor .
FLT3 mutations are identified in about onethird of adult acute myeloid leukemia . The interactions between the vascular endothelial growth factors and their receptors are crucial for angiogenesis. The expression of VEGF and its receptors are detected in most of solid tumors and hematological malignancies. Overexpression of VEGF and or it,s receptor VEGFR2 contributes to invasiveness and metastasis of breast, lung, prostate, renal cell, colon cancers and hepatocellular carcinoma. In AML, a number of studies have demonstrated that an autocrine paracrine pathway between VEGF and its receptors are involved in poor survival of a subset of patients and progression of the disease.
This evidence underpins an important discovery in the molecular biology of cancer that histological different types of cancer could share the same dysregulated signaling pathway and one particular type of cancer could have multiple genetic abnormalities. Therefore, there has been great interest in discovering compounds targeting multiple RTKs with the rationale of potential superior antitumor activity for a variety of cancer types. ABT 869, a novel ATP competitive RTK inhibitor, is active against all VEGFRs and PDGFR families, but minimally active against unrelated RTKs and cytosolic tyrosine kinases and serine threonine kinases. The goals of this article are to s