3 cancers causing most deaths in men vs women:
Men=lung + liver + stomach
Women=breast + lung + colorectal
Why does lung cancer cause do many deaths?
detected late
Cancer is a disease of the….
genome
4 examples of genetic mutations that can cause cancer:
Chromosomal translocations
Point
deletion/insertion
epigenetic alterations
4 main cancer treatments:
surgery
chemotherapy
radiotherapy
immunotherapy
2 types of chemotherapy drugs:
targeted
cytotoxic
What are the 2 types of targeted therapies?
monoclonal antibodies
small molecule inhibitors
Name all the cytotoxic chemotherapy drugs:
Alylating agents Pseudoalkylating agents antimetabolites anthracyclines topoisomerase inhibitors
What do all the cytotoxic chemotherapy drugs apart from taxanes/vinca alkaloids target?
intrinsic DNA
So we know taxanes/vinca alkaloids put cells in long term mitotic arrest but how?
microtubules
How are cytotoxic chemotherapy drugs administered?
IV/oral
Where do cytotoxic chemotherapy drugs work?
systemic-work on all cells
Why is a side effect of chemotherapy drugs ulcers + bone marrow suppression?
cells that divide more rapidly will be proportionally more effected e.g. stomach epithelium + bone marrow
What is a neo-adjuvant?
given before surgery to try and downstage the cancer
What is adjuvant chemotherapy?
given after surgery to get rid of any cancer cells not removed during surgery
How do alkylating agents work?
add alkyl groups to guanine residues which causes them to crosslink meaning they can’t uncoil during replication which triggers+ apoptosis
How do pseudo alkylating agents work?
add platinum to guanine residues
How do anti-metabolites work?
purines/pyrimidine residues that inhibits DNA replication + cause strand breaks–>apoptosis
Side effects of all cytotoxic chemotherapy drugs?
loss of hair
nausea
vomiting
How do anthracyclines work?
block DNA repair
Inhibit transcription
Create oxygen radicals
What is the main side effect of anthracyclines?
cardiac toxicity
How do topoisomerase inhibitors work?
inhibit topoisomerase which is an enzyme that prevents DNA torsional strain=strand breaks
3 ways resistance to chemotherapy might form?
Pumps to efflux drug
PARPs-remove DNA adducts
Enhanced DNA repair
‘Self sufficient’ is one of the hallmarks of cancer, what does it mean?
can stimulate cell proliferation without need for stimuli i.e. growth factors
How do monoclonal antibodies work?
stop dimerisation of receptors and dowstream signalling/internalisation of receptors
How do small molecule inhibitors work?
bind to kinase domains + stop downstream signalling
What is a huge advantage of targeted chemotherapy drugs?
not systemic
