biological basis of cancer therapy

Question 1

main types of anti-cancer treatment

Answer 1

surgery, radiotherapy, chemotherapy, immunotherapy

Question 2

what kinds of mutations cause cancer

Answer 2

translocation, deletion/insertion, point mutations, epigenetic changes

Question 3

systemic therapy- types and what is attacked

Answer 3

cytoxic chemotherapy (alkylating agents, topoisomerase inhibitors, antimetabolites and anthracyclines attack tumour DNA, vica alkaloids/taxans attack microtubules) target therapies (monoclonal antibodies, small molecule inhibitors)

Question 4

cytotoxic chemotherapy- what it affects, how its given

Answer 4

given orally/intravenously- affects all rapidly dividing cells in body ie SYSTEMIC adjuvant therapy given after operation as an insurance policy

Question 5

alkylating agent- how it works and problem

Answer 5

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

Question 6

pseudo-alkylating agents

Answer 6

adds platinium to guanine, NOT alkyl group- has same effect- drugs end in PLATIN

Question 7

anti-metabolites- mechanism plus side effects

Answer 7

purine/pyramidine preventing DNA synthesis hair loss, bone marrow surpression ie anaemia/ infection risk, neutropenia nausea and PPE (skin begins to peel)

Question 8

anthracyclines- mechanism and side effects

Answer 8

inhibit transcription/replication by inserting a nucleotide- blocks DNA repair as well cardiac toxicity, hair loss, red urine, neutropenia

Question 9

vinca alkaloids and taxanes+ side effects

Answer 9

block assembly microtubules= mitotic arrest nerve damage, hair loss, nausea, bone marrow surpression

Question 10

topoisomerase inhibitors + side effects

Answer 10

these enzymes needed to prevent DNA torsional strain during replication cholinergic syndrome eg diarrhoea (give atropine as well)- also hair loss+ bone marrow surpression

Question 11

ovarian cancer- response rates to cytotoxics

Answer 11

has increased ie more successful

Question 12

resistance to chemotherapy

Answer 12

DNA repair upregulated, drug can be effluxed from cell by ABC transporters as well

Question 13

hallmarks of cancer

Answer 13

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

Question 14

over-expression in cancer with examples

Answer 14

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

Question 15

how monoclonal antibodies work

Answer 15

target extracellular component of receptor- receptor can’t form dimer, and ligand is neutralised

Question 16

how small molecule inhibitors work and example

Answer 16

bind to kinase domain of receptor tyrosine kinase= no phosphorylation: also block INTRACELLULAR kinases Glivec binds to ATP binding region in kinase domain

Question 17

monoclonal vs small molecules

Answer 17

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

Question 18

resistance to target therapies

Answer 18

mutation in ATP binding domain, downstream pathways upregulated

Question 19

newer therapies

Answer 19

anti-sense oligonucleotides- single stranded DNA like molecules, preventing translation and cleaving mRNA RNA interference