Biological basis Of Cancer Therapy Flashcards

1
Q

Main ways of treating cancer

A

Surgery
RT
CT
Immunotherapy

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2
Q

Types of genetic mutations causing cancer

A
Chromosome tanslocations
Gene amplification 
Point mutations within promoter or enhancer regions
Deletions or insertions
Epigenetic alterations
Inherited
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3
Q

What is systemic cytotoxic therapy?

A

Can be given IV or orally
Not targeted
Acts on all rapidly dividing cells in body eg. Gut mucosa

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4
Q

What are alkylating agents?

A

Add alkyl groups to guanine residues to cause crosslinking of DNA leading to death.
Cant uncoil during replication
Trigger apoptosis
E.g chlorambucil

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5
Q

Pseudo alkylating agents

A

Add platinum to guanine residues causing cell death

E.g. cisplatin, carboplatin

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6
Q

Cisplatin MOA

A

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

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7
Q

How do anti metabolites work

A

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)

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8
Q

MOA of gemcitabine

A

Can block DNA synthesis when phosphorylated

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9
Q

Side effects of most drugs

A
Alopecia
Bone marrow suppression
Neutropenia
Bleeding
Nausea and vomiting 
Diarrhoea
Fatigue
Skin changes
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10
Q

How do anthracyclines work?

A

Inhibit transcription and replication by inserting between nucleotides
Create damaging O2 radicals
Causes red urine

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11
Q

How do vinca alkaloids and taxanes work

A

Natural sources originally
Initiate assembly or dissasembly of mitotic microtubules = mitotic arrest
Can cause nerve damage

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12
Q

How to topoisomerase inhibitors work

A

Induce temporary single strand or double strand breaks in DNA backbone
Eg. Topotecan, etoposide
Normally given with atropine due to severe cholinergic type syndrome

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13
Q

General ways cells become resistant

A

Upregulated dna repair mechs

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14
Q

Cisplatin resistance

A
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)
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15
Q

How can you overcome resistance

A

Increase local delivery of drug
Liposome delivery systems
More water soluble platins that diffuse into cell

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16
Q

How is GFR targeted in therapy

A

Target tyrosine kinase pathways

17
Q

2 examples of an over expressed kinase receptor and how to target

A

HER2 - BC
EGFR - BC and colorectal
Use monoclonal antibodies

18
Q

MOA of monoclonal antibodies

A

Neutralise ligands, prevents receptor dimerisation, no downstream signalling
Activates phagocytosis, complement

19
Q

How else can we target TK receptors

A

Small molecule inhibitors eg. Imatinib

Bind to kinase domain and block auto phosphorylation and downstream signalling

20
Q

Resistance mechanisms to targeted therapies

A

Mutations in ATP binding domain
Intrinsic resistance
Intragenic mutations
Up regulation of downstream parallel pathways

21
Q

What is the difference between anti sense oligonucleotides and RNAi?

A

Both targeted therapies which use genetic info
ASO are modified DNA like molecules, hybridise to target gene and hinder translation or specific mRNA.
Recruits RNase to cleave mRNA
RNAi is complementary to RNA (see epigenetics)

22
Q

B raf success story

A

Activating mutations found in 60% of melanomas

B raf inhibitor extends life span for 7 months