Multiple Meyloma Tallahassee Cancer Institute多发性骨髓瘤塔拉哈西癌症研究所.pptVIP

MM BMSC TNFα TGFβ VEGF IL-6 IL-6 VEGF IGF-1 SDF-1α NF-KB Interaction of MM cells and their BM milieu MEK/ERK GSK-3β FKHR Caspase-9 NF-KB mTOR Bad PKC Akt migration JAK/STAT3 LFA-1 VCAM-1 Fibronectin ICAM-1 NF-KB MUC-1 VLA-4 Adhesion molecules Proliferation Anti-apoptosis Survival Anti-apoptosis Cell cycle Proliferation p27Kip1 Survival Anti-apoptosis Cell cycle PI3-K NF-KB ERK Smad2 Bcl-xL IAP Cyclin-D Bcl-xL MCL-1 MEK/ERK Survival Anti-apoptosis Myeloma Cells and BM Microenvironment Bruno et al, The Lancet Oncology, July 2004, 430-442 Apoptotic Signaling Pathways Velcade ZME-2 Dex ImiDs, Velcade HDAC-I, 2ME-2 TNFα FasL TRAIL JNK Caspase-9 Caspase-8 Caspase-3 PARP Apoptosis IL-6 IGF-1 Smac Cytochrome-c Bid FADD Mitochondria Hideshima et al, Blood, August 2004, 607-618 Novel biologically based therapies targeting MM cells and the BM microenvironment A D C B Angiogenesis Adhesion Molecule Drug Resistance Proliferation Apoptosis Growth Arrest Inhibition of Adhesion Inhibition of Cytokines bFGF VEGF IL-6 IGF-1 VEGF SDF-1α Novel Agents Novel Agents for Myeloma Targeting both MM cells and interaction of MM cells with the BM microenvironment Targeting circuits mediating MM cell growth and survival Targeting the BM microenvironment Targeting cell surface receptors Novel Agents for Myeloma Thalidomide and its analogs (Revlimid) Proteasome inhibitor (Bortezomib) Arsenic trioxide 2-Methoxyestradiol (2-ME2) Lysophosphatidic acid acyltransferase-β inhibitor Triterpinoid 2-cyano-3, 12-dioxoolean-1, 9-dien-28- oic acid (CDDO) N-N-Diethl-8, 8-dipropyl-2-azaspiro [4.5] decane-2-propanamine (Atiprimod) Targeting both MM cells and their interaction with BM microenvironment Targeting circuits mediating MM cell growth and survival VEGF receptor tyrosine kinase inhibitor (PTK787/ZK222584, GW654652) Farnesyltransferase inhibitor Histone deacetylase inhibitor (SAHA, LAQ824) Heat shock protein-90 inhibitor (Geldanamycin,17-AAG) Telomerase inhibitor (T