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제107회 대한화학회 학술발표회, 총회 및 기기전시회 Roles of Two Major Tyrosine Kinase Receptors- VEGFR2 and Tie2 in Tumor Angiogenesis

2011년 3월 16일 12시 01분 39초
MEDI-1 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 14시 : 00분
의약화학 - Current Trend and Future in Cardio Vascular Disease
저자 및
KAIST 의과학대학원, Korea
Two major tyrosine kinase receptors ? VEGFR2 and Tie2 are mainly expressed in blood endothelial cells and promote angiogenesis during embryonic development and pathologic processes including tumor. Five VEGFR ligands have been identified: VEGF-A, VEGF-B, VEGF-C, VEGF-D and placental growth factor (PlGF). VEGF-A interacts with both VEGFR-1 and VEGFR-2 to mediate angiogenesis, whereas VEGF-B and PlGF have high affinity to VEGFR-1 but do not promote angiogenesis. VEGF-C and VEGF-D bind to both VEGFR-2 and VEGFR-3 to promote angiogenesis and lymphangiogenesis. Various strategies for inhibiting the VEGF-VEGFR signaling pathways have been investigated over the last decade. These include neutralizing antibodies to VEGF-VEGFR, low-molecular- weight VEGFR tyrosine kinase inhibitors (e.g. sunitinib) and soluble VEGFR1 constructs (e.g., VEGF-Trap). These reagents are currently used to inhibit tumor angiogenesis for patients with various cancers. However, resistance and tumor invasion to these drugs are serious problems in the oncology clinic. Moreover, no biomarker for these drugs is currently available. Two Tie receptors have been identified: Tie1 and Tie2. No specific ligand to Tie1 has been identified. In comparison, angiopoietins are potent and selective protein molecules targeted to mainly Tie2. Angiopoietins include four proteins: Ang-1, -2, -3, and -4. Traditionally, Ang-1 and Ang4 act as agonists to Tie2, whereas Ang2 and Ang3 act as antagonists to Tie2. However, recent accumulating evidences indicate that Ang2 and Ang3 also act as agonists to Tie2 in a context-dependent manner. Various strategies for inhibiting angiopoietins-Tie2 signaling pathways have been developed over the last decade. These include anti-Ang2 antibody, antagonistic peptibody of Ang2, soluble Tie2-Fc and double anti-angiogenic protein (DAAP). These reagents are currently testing to inhibit tumor angiogenesis in the preclinical animal models.