Cancer 3: Biological basis of cancer therapy Flashcards
what are the 4 main anti-cancer modalities?
Surgery, chemo, radio and immunotherapy (much rarer-gaining tho)
What kind of mutations can lead to cancer?
Translocation, amplification, point mutations, deletions, insertion, epigenetics, can be inhited-but usually combinations found
So want to target the damaged genome- but not kill the healthy cells
What types of systemic therapy are there for chemotherapy
Cytotoxic-systemic -Akalytin, antimetabolites, anthacyline, vinca alkaloids, taxanes, toposiomerase
usually given IV or oral
work systemically-target all rapidly dividing cells in bode (like Bone marrow cell, skin, hair, mucin cells)
given post operativly-adjuvant-reduce chances of coming back
Pre-op-neoadjuvantly-increases chances of surgery
Can be monotherapy or combination
can be curative or palliative (not die immediatly-but at some point)
Targetted-small molecule inhbitors, monoclonal AB
How do alkylating agents work as chemi?
Add alkyl groups to Gyanine in DNA-cross link the DNA strands and prevents DNA from uncoilling
Trigger apoptosis via checkpoints
Pseudoalkylating agents add platinium instead of alkyl to G but act the same way overall
eg: Dacarbazine, Pseudo-carboplatin
Side effect-hair loss, nephrotoxic, neurotoxic, ototoxicity, nausea, vomiting, diarhhoae
How do anti-metabolites work for chemo?
Fake purine/pyrimidine analogues/ or folate analogue-but doent work as proper-stops DNA synthesis
eg: metotrexate
side effects; yes
Anthracycline in Chemo?
Intercaate nucleotides between DNA/RNA strands
Side effects: cardiac toxic (rare), alopecia, neutropenia, nausea and vom, fatigue, skin, red urine
Vinca Alkaloids/taxanes in chemo?
originally from natural sources-make cell go to mitotic arrest
Prevents assembly or dissasembly of microtubules
Side effect: nerve damgage, ANS dysfunction, hair loss, all the normal
Topiosiomerase inhbitors in chemo?
Required to open up DNA to duplicate-inhbitor stops the binding properly-cause permanant DNA damage when bind
eg; Irinotecan
side: Acute cholinergic symptoms-fight with atropine
Hair loss, nausea, vom, fatigue, BM dysnfunction
what is the main side effect of chemotherapy?
Neutropenic sepsis-loss of WBC-can be very dangerous with infections-so able to get ABx within 1h if necessary
Can cancer become resistant to cytotoxic chemotherapy?
Yes-enchanced DNA repair
Can use PARPs-remove the DNA addups and repair
Or transporters to remove the drugs from the cell
How do targetted chemotherapy work?
in rare monogenic cancer can cut a wire-and stop it
but usually cause upregulation of another one
Now era of dual-kinase inhbitors-cut more than one “wire”
How can cancer cells become self sufficient
Self sufficient-no need for external GF to proliferate (receptor TK eg: Her2 in breast cancer-overexpression of the receptor (also EGFR)). can also get overexpression of ligan (VEGF), and can have ligand independent receptor activation
How do monoclonal AB help target self sufficient cancer cells
Can be from mouse/hydridiseed/humanised or human Ab
usually target extracellular end of receptor-prevent ligand binding and/or dimerisation -can also cause internalisation of receptor, or activate complement+immune system
eg: Cetixumab-target EGFR
What are small molecule inhbitors and how can they help cure cancer?
Bind to the intracellular part of tyrosine like receptor–prevent from it signalling or more
can also target parts of the cascade after the signallin
Eg: Glivec-in CML- BCR-Abl translocation cause the cancer-drug can target it well-and stop the cancer form being overactive-targets the ATP binding domain of RTKL-
What are advantages/disadvatages or AB vs small molecule inhbitors
AB-specific, cause immune activity, long half life, good for heamoatology
bad: expensive, complex, cant get to every tissue, IV
Small molecule-cheap, can be oral, good tissue penetration
-not super specific, oral-can be degraded, idk anymore ffs
Resistance if the main problem for both anyways
