proliferaton, differentiation, invasiveness, metastasis
Targets for anti cancer drugs exploiting difference between host and tumour:
angiogenesis, immune response, inflammation
Targets for anti cancer drugs using host mechanisms:
Therapeutics for cancer usually rely on ...differences a reason for their highly dose dependent effects
bone marrow, immune, GI epithelia, growth, fertility, nausea
Most chemotherapeutic drugs effect these systems
hyperplasia, anaplasia, invasiveness, metastasis
Characteristics of cancers:
proto oncogenes, tumour supressor genes
Transformation to a tumour occurs via activation of... and inactivation of...
mutation, chromosome rearrangement, viral transduction
Genetic changes causing transformation
GF, GFRs, Signal transduction, TFs
Examples of proto-oncogenes
The percentage of actively dividing cells in a tumour
As a tumour increases in size its growth fraction ....
stage of the cell cycle
Many chemotherapeutics are dependent upon the cell being in the correct ....
There is little immune response to a tumour as it is
Cancer mutations in response to drug treatment often results in ....
Treating very specific cell types is not a good strategy due to...
group of drugs causing cross linking of DNA strands
cisplatin, nitrogen mustards
Examples of alkylating agents
inducing mutation, halting DNA synthesis
alkylating agents stop growth by...
increase DNA repair, increase drug metabolism, decrease drug permeability
methods of resistance to alkylating agents
Methotrexate, 5' fluorouracil
Examples of anti metabolites
inhibiting dihydrofolate reductase, tetrahydrofolate
MTX works by .... preventing the synthesis of.... resulting in decreased production of purine nucleosides
S phase, rapidly dividing
MTX works specifically during the... of the cell cycle and thus targets ...cells
MTX results in a lack of ... thus DNA replication cannot continue
inhibiting thymidylate synthase, thymidine
5' flurouracil works by .... preventing synthesis of ...
Example of an intercalating anti cancer drug
stabilising topoisomerase II, broken
Doxorubicin works by...... causing the DNA chain to be ...
decreased affinity for DHFR, increased [DHFR], reduced IC transport
resistance to MTX may occur via...
Example of a plant alkaloid used in cancer therapy
inhibits microtubule assembly
Taxol works as it....
reduced spindle formation, reduced cell migration
Taxol reduces microtubule assembly thus causing.... and... which is bad!
Strategy to avoid one hit resistance of cancers...
toxic, complex, expensive
Problems with combination therapy...
Example of a AB treatment
Trastuzamab AB targets ...
one hit resistance
Specific treatments such as ABs are suceptable to...