novel therapeutics Flashcards
cytokines
1980’s
Interferon
Interleukin 2
Effect only proven in renal cell cancer
Some low grade lymphomas
growth factors
Granulocyte colony stimulating factor G-CSF
Reduction in neutropenic sepsis
Mobilisation of bone marrow stem cells
S.c. injection daily
Mild flu like symptoms
growth factor receptor inhibition
bevacuzimab - anti-ligand mAbs
Herceptin and cetuximab - anti-receptor mAbs
Tyrosine kinase inh - ATP and sub competitors
monoclonal antibodies
cetuximab chimeric anti EGFR Mab
Kohler & Milstein Mab
Waldman & Winter humanised antibody
Campath-1H : CLL
Mabthera : NHL
Herceptin : Breast ca
Cetuximab : EGFR in colorectal, H&N,lung..
Bevacuzimab: VEGF
egfr therapeutics
herceptin
EGFR inhib
Gene amplification and overexpression of her-2 in 20% breast cancer
Trastuzumab (herceptin) is a chimeric MAb against her2 trans-membrane growth factor receptor
In metastatic disease, 35% RR in her2 + ca
5 trials now show a 50% reduction in relapse rate in her2 + early breast cancer (2005)
cetuximab
IgG1 monoclonal antibody
Exclusive for EGFR and its heterodimers
Prevents ligand binding to EGFR
Higher affinity for EGFR compared to natural ligands
Blocks receptor dimerization, tyrosine kinase phosphorylation, signal transduction
Stimulates receptor internalization
Fc region may induce antibody-dependent cell-mediated cytotoxicity (ADCC) (immune response)
vegf
avastin
VEGF inhibitor
ptk/zk
tyrosine kinase inhibition: TKIs
tyrosine kinase ihibitors
Multiple TKs in cell signal transduction pathways
Able to design specific inhibitors of enzymatic function
First active agent designed for CML
imatinib
1960s Philadelphia chromosome
1973 Balanced translocation t(9:22)
1983 bcr-abl fusion gene
1984 tyrosine kinase enzyme activity increases cell survival, decreases cell death and adhesion
1992 specific inhibitor manufactured STI 751 (Novartis)
