kinases and cancer Flashcards
what are the 6 hallmarks of cancer?
- self-sufficiency in growth signals
- insensitivity to antigrowth signals
- sustained angiogenesis
- tissue invasion and metastasis
- limitless replicative potential
- evasion of apoptosis
what do conventional cancer therapies aim to do?
target generic properties of cancer cells such as rapid proliferation
- cytotoxic agents, radiotherapy
- surgery
what do ‘modern’ cancer therapies aim to do?
tagret properties of cancer such as specific receptors or key proteins that are dysregulated
- monoclonal antibodies
- kinase inhibitors
what are seven potential ways of interefering with cancer cells?
- signalling molecules
- signal receptors and intracellular receptors
- intracellular transducers
- transcription factors
- apoptotic proteins
- cell cycle control proteins
- DNA repair proteins
what are the two genetic basis’s of cancer?
1) Gain of function mutations convert proto-oncogenes into oncogenes
2) tumour supressor genes
name the three possible GOF mutations of cancer that convert proto-oncogenes to oncogenes?
- point mutation
- chromosomal translocation
- amplification
what is a point mutation?
single base pair change leaving protein constitutively active
what is chromosomal translocation?
- results on hybrid gene with uncontrolled activity
- growth regulatory protein under control of different promoter causing inappropriate expression of the gene
what is amplification ?
multiple DNA copies causing overproduction of respective protein
what kinases are prominent members on the mutated list?
- receptor tyrosine kinases (RTK) eg. EGF/ ERB
- cytosolic kinases eg. src
- nuclear kinases eg. Jun Fos
What is a parakine ErbB stimulation
ERB ligand released from stromal cells
what is autokrine ErbB stimulation
ER, GPCR or FZD stimulation activates metalloproteinase cleaving Pro-ERBB liganda
What are the two interventions ideas?
1) Inhibit dimerisation of EGF/ ErbB receptors to suppress proliferation signal
2) Inhibit kinase activity using small molecule tyrosine kinase domain inhibitors
