biological basis of cancer therapy Flashcards
main types of anti-cancer treatment
surgery, radiotherapy, chemotherapy, immunotherapy
what kinds of mutations cause cancer
translocation, deletion/insertion, point mutations, epigenetic changes
systemic therapy- types and what is attacked
cytoxic chemotherapy (alkylating agents, topoisomerase inhibitors, antimetabolites and anthracyclines attack tumour DNA, vica alkaloids/taxans attack microtubules) target therapies (monoclonal antibodies, small molecule inhibitors)
cytotoxic chemotherapy- what it affects, how its given
given orally/intravenously- affects all rapidly dividing cells in body ie SYSTEMIC adjuvant therapy given after operation as an insurance policy
alkylating agent- how it works and problem
adds alkyl group to guanine in DNA, preventing DNA uncoiling= apoptosis can lead to secondary malignancy- also hair loss, nausea, potentially toxic to kidney/nerves
pseudo-alkylating agents
adds platinium to guanine, NOT alkyl group- has same effect- drugs end in PLATIN
anti-metabolites- mechanism plus side effects
purine/pyramidine preventing DNA synthesis hair loss, bone marrow surpression ie anaemia/ infection risk, neutropenia nausea and PPE (skin begins to peel)
anthracyclines- mechanism and side effects
inhibit transcription/replication by inserting a nucleotide- blocks DNA repair as well cardiac toxicity, hair loss, red urine, neutropenia
vinca alkaloids and taxanes+ side effects
block assembly microtubules= mitotic arrest nerve damage, hair loss, nausea, bone marrow surpression
topoisomerase inhibitors + side effects
these enzymes needed to prevent DNA torsional strain during replication cholinergic syndrome eg diarrhoea (give atropine as well)- also hair loss+ bone marrow surpression
ovarian cancer- response rates to cytotoxics
has increased ie more successful
resistance to chemotherapy
DNA repair upregulated, drug can be effluxed from cell by ABC transporters as well
hallmarks of cancer
self-sufficient, doesn’t respond to anti-growth signals, metastatic, pro-angiogenic, non-senescent ie wont die also has unregulated metabolism, avoids immune system, causes inflammation
over-expression in cancer with examples
receptors that respond to growth factors often in excess in cancers eg HER2 in breast, EGFR in breast/colorectal cancer= increased kinase cascade also overexpression of ligand eg VEGF in prostate cancer
how monoclonal antibodies work
target extracellular component of receptor- receptor can’t form dimer, and ligand is neutralised
how small molecule inhibitors work and example
bind to kinase domain of receptor tyrosine kinase= no phosphorylation: also block INTRACELLULAR kinases Glivec binds to ATP binding region in kinase domain
monoclonal vs small molecules
antibodies are very specific, cause immune response and long half life however, can cause allergy, are often large as well small molecules are cheaper and can target ligand independent kinase but shorter half life and more frequently administered
resistance to target therapies
mutation in ATP binding domain, downstream pathways upregulated
newer therapies
anti-sense oligonucleotides- single stranded DNA like molecules, preventing translation and cleaving mRNA RNA interference
