Biologic Targeting in RT

arunmp's version from 2016-12-21 09:02

Biologic Targeting in RT

Features of Carcinogenesis- short note-what happesns to each
Question Answer
Mutations with gain in function for(oncogenes)
Mutations with loss of function(tumor suppressor genes)
Mutations affectAffect molecular signaling pathways and causes
• (overexpression of ligands or receptors associated withself-sufficient growth factor signaling
• Loss of response to anti-proliferative signals
• Evasion ofcell death programs
• Increase inreplicative potential (telomeres)
• Promotion of tissue invasion and metastasis
• Sustained angiogenesis
• abnormalitiesDNA repair and genomic instability


Question Answer
• Activation of cell cycle progression and survival pathways generally increasesradioresistance
• Activation of pro-apoptotic/cell cycle arrest pathways generallyradiosensitize


Question Answer
Imatinib (Gleevec)Bcr-Abl, c-kit, PDGFR-a
Gefitinib (Iressa)EGFr
Erlotinib (Tarceva)EGFR
Bortezomib (Velcade)Proteasome
Sorafenib (Nexavar)c-Raf, BRA, Kit, EGFR
Sunitinib (Sutent)Multiple RTKs, VEGF, PDGF
Dasatinib (Sprycel)BCR-ABL, SRC family,
Bevacizumab (Avastin)VEGF
Alemtuzumab (Campath)CD52
Cetuximab (Erbitux)EGFR (HER-1)
Trastuzumab (Herceptin)HER2
Tositumomab (Bexxar)CD20
Rituximab (Rituxan )CD20
Ibritumomab tiuxetan (Zevalin)CD20
Gemtuzumab (Mylotarg)CD33
Panitumumab(Vectibix) : EGFR
Question Answer
Lapatiniboral tyrosine kinase inhibitor of ErbB1 and ErbB2 NEOALTO TRIAL


Multiple target thera
Question Answer
Dual kinase Inhibitor EGFR/VEGF Inhibitors Tyrosine Kinase Inhibitors- Vandatanib (ZD6474)
Dual kinase Inhibitor EGFR/HER 2 InhibitorsTyrosine Kinase Inhibitors- Lapatinib
Multi kinase InhibitorVEGFR, PDGFR, KIT and FLT3RTyrosine Kinase inhibitor- Sunitinib
Multi kinase InhibitorVEGFR2 and VEGFR3, FLT-3, PDGFR, c-KITTyrosine Kinase Inhibitor- Sorafenib
Sorafenib is an oral inhibitor of RAF


Question Answer
Most molecular targeting agents are likely to be more cytostatic than cytotoxic, and are unlikely to be curative and adjuvant therapy with RT than radical
Imatinib (Gleevec) CML, GIST
Gefitinib (Iressa)NSLC-10% respond
Erlotinib (Tarceva)NSLC, mesothelioma
Bortezomib (Velcade)Multiple myeloma 1 year 23% of patients
Sorafenib (Nexavar)mRCc FLT-3, VEGFR, PDGFR-β
Sunitinib (Sutent)GIST and mRCC GIST: 25.5% MRCC: 36.5%
Dasatinib (Sprycel)CML and Ph+ ALL
Bevacizumab (Avastin)CRC,5 months prolonged survival,GBM, Her2/neu negative metastatic breast cancer,mrcc,metastatic adeno ca lung
Alemtuzumab (Campath)B-cell CLL ,9.5 months 30% patients
Cetuximab (Erbitux)CRC, pancreatic Ca increased response HNSCC, NSLC
Trastuzumab (Herceptin)HER2 Breast cancer 25 months for 26%
Tositumomab (Bexxar)NHL 57% to 71% respond
Rituximab (Rituxan )NHL, CLL,MM, HCL 3 months in 45% of patients
Ibritumomab tiuxetan (Zevalin)NHL 80% respond
Gemtuzumab (Mylotarg)AML 6 months 30% of patients
Panitumumab(Vectibix) : Mcolorectalrc with kras+ PFS 96 days
Question Answer
Non-selective COX I and 2 inhibitorsNSAIDs - aspirin, ibuprofen, indomethacin -
Selective COX2 inhibitorscelecoxib, rofecoxib, meloxicam, NS-398, etc


Question Answer
Exploiting Low Tumor Oxygenation with Hypoxic CytotoxinsTripazapmine
NF-kB is activated which transcribes anti-apoptotic factors inhibitors of apoptosis (IAPs) like survivin, Bcl-XL, etc