Biological basis Of Cancer Therapy Flashcards
Main ways of treating cancer
Surgery
RT
CT
Immunotherapy
Types of genetic mutations causing cancer
Chromosome tanslocations Gene amplification Point mutations within promoter or enhancer regions Deletions or insertions Epigenetic alterations Inherited
What is systemic cytotoxic therapy?
Can be given IV or orally
Not targeted
Acts on all rapidly dividing cells in body eg. Gut mucosa
What are alkylating agents?
Add alkyl groups to guanine residues to cause crosslinking of DNA leading to death.
Cant uncoil during replication
Trigger apoptosis
E.g chlorambucil
Pseudo alkylating agents
Add platinum to guanine residues causing cell death
E.g. cisplatin, carboplatin
Cisplatin MOA
Enters through Copper channels
Binds to guanine and cross links
Can cause:
Nucleotide excision repair leading to p53 activation
Mismatch repair pathway leading to p53 activation
How do anti metabolites work
Masqueraded as purines or pyramidines or folate antagonists
Inhibit DNA synthesis
Cause double strand breaks and apoptosis
Block DNA replication and transcription
Inhibit folic acid production (important for nucleic acid production)
MOA of gemcitabine
Can block DNA synthesis when phosphorylated
Side effects of most drugs
Alopecia Bone marrow suppression Neutropenia Bleeding Nausea and vomiting Diarrhoea Fatigue Skin changes
How do anthracyclines work?
Inhibit transcription and replication by inserting between nucleotides
Create damaging O2 radicals
Causes red urine
How do vinca alkaloids and taxanes work
Natural sources originally
Initiate assembly or dissasembly of mitotic microtubules = mitotic arrest
Can cause nerve damage
How to topoisomerase inhibitors work
Induce temporary single strand or double strand breaks in DNA backbone
Eg. Topotecan, etoposide
Normally given with atropine due to severe cholinergic type syndrome
General ways cells become resistant
Upregulated dna repair mechs
Cisplatin resistance
Down regulation of copper channels Less cisplatin in cell Cisplatin in cell mopped up and effluxed Upregulation of repair proteins Overexpression of anti apoptotic proteins (akt)
How can you overcome resistance
Increase local delivery of drug
Liposome delivery systems
More water soluble platins that diffuse into cell