Bevacizumab is -

Ans. is 'a' i.e., Anti VEGF antibody These new molecular targeted agents are very important -Tyrosine kinase inhibitorsAs explained in previous question. Tyrosine kinase overactivity can be inhibited by1. Direct inhibiton of nonreceptor tyrosine kinaseo Imatinibo Basatinibo Nilotinin}- used in CMLNote - Imatinib also inhibits tyrosine kinase activity of PDGF, stem cell receptor and C-Kit receptor found in GIST.2. Blocking of growth factors that increase tyrosine kinase activity',o EGF inhibitorsCompetitive inhibitors- Gefitinib, erlotinib - used in nonsmall cell lung Ca.Monoclonal antibodies- Panitumomab, cetuximab - used in colon Ca.o VEGF, PDGF and C-Kit inhibitors# Sunitinib and sorafinib are used in renal cell carcinoma (in RCC there is overexpression of VEGF) and GIST (in GIST there is over expression of C-Kit & PDGF).B. HER2 / neu (ERBB2.) inhibitorso There is overexpression of HERy'neu in breast cancer.o Trastuzumab is a monoclonal antibody against HER./neu gene product - used in breast cancer.C. Targeted antibody against cell surface moleculeo Rituximab (anti CD-20) - used in B-cell lymphoma that express CD-20,o Alemtuzumab (anti CD-56) - in CLL and CD-56 expressing lymphoid tumors.D. Anti vascular endothelial growth factor (VEGF) antibodyo VEGF promotes angiogenesis in many tumors.o Bevacizumab (monoclonal anti VEGF antibody) can be used in colon, lung, breast cancers.E. Proteosome inhibitorso Transcription factor IS'FKB is associated by an inhibitor IKB.o 1KB is degraded by proteosomes.o Inhibition of proteosome prevents degradation of IKB w'hich inhibits the overactivity of NFKB.o Proteosome inhibitor (Bartezomib) is used in multiple myeloma.F. Histone deacvlase inhibitorso Acetylated histones (H3 & H4) promote transcription initiation,o Histone deacetyiases cause deacetylation of histone & repress this effect.o Vorinostat is an inhibitor of histone deacetyiases, maintains the acetylated state of histone - acetylated histones allow entry of transcription factors and therefore expression of genes that are selectively repressed in tumours.o Vorinostat is used in cutaneous T-cell lymphoma.G. DNA methyl transferase inhibitorso Hvpermethylation of cytosines in promoter regions is a common mechanism by which tumor suppressor loci are epigenetically silenced in cacer.o DNA methyl transferase inhibitors increase transcription of genes, "silenced" during the pathogenesis of tumor, by causing demethylation of methylated cytosines.o These drugs, 5-azacytidine, 2-deoxy-5-azacytidine, can be used in myelodysplasia and some leukemias,o Decitabine is also an methyl transferase inhibitorH. Biological response modifiero Recombinant IL-2 (Ialdesleukin, denileukin) are used in renal cell carcinoma.o Denileukin deftiiox is a combination of IL-2 with diphtheria toxin - used for cutaneous T cell lymphoma.I. All-trans-retinoic acido Used in acute promyeiocytic leukemia (APL).o In majority of APL, there is generation of PML - RAR fusion protein.o This PML-RAR fusion protein binds to promoters containing retinoic acid response elements and recruits histone deacetylases (HADAs).o HADAs deacetylate histones (H3. & H4) and repress the initiation of transcription,o This arrests differentiation at promyeiocytic stage.o Treatment with all-trans-retinoic acid, which is a ligand for RAR, results in release of HADAs and overcomes the differentiation block.