Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CANKER - OBG > Biological Basis of Cancer Therapy > Flashcards

Biological Basis of Cancer Therapy Flashcards

1
Q

What are the five most common cancers worldwide?

A 
1st- Lung (in men)
1st - Breast  (in women)
western: 
Bowel 
Prostate  
Stomach
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the four main anti-cancer modalities?

A

Radiotherapy

Chemotherapy

Surgery

Immunotherapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the different types of cytotoxic chemotherapy.

A

Alkylating agents

Pseudoalkylating agents

Antimetabolites

Anthracyclines

Vinca alkaloids and taxanes

Topoisomerase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the main types of targeted therapy for cancer?

A

Monoclonal antibodies

Small molecule inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

hat is the term used to describe chemotherapy that is given:

a. Following surgery
b. Before surgery

A

a. Adjuvant

b. Neoadjuvant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do alkylating agents work?

A

They add an alkyl group to the guanine residues in DNA

This causes cross-linking of the DNA strands and prevents DNA from uncoiling at replication

This then triggers apoptosis (via a DNA checkpoint pathway)

It encourages mis-pairing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Name 3 alkylating agents.

A

Chlorambucil

Cyclophosphamide

Dacarbazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How do pseudoalkylating agents work?

A

They have the same mechanism as alkylating agents but use platinum instead of alkyl groups

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Name three pseudoalkylating agents.

A

Carboplatin
Cisplatin
Oxaliplatin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are some side effects of alkylating and pseudoalkylating agents?

A 
Alopecia (except carboplatin), 
  Nephrotoxicity, 
Neurotoxicity,  
Ototoxicity (platins), 
Nausea, Vomiting, Diarrhoea, Immunosuppression,  Tiredness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do anti-metabolites work?

A

They masquerade as purine or pyrimidines leading to inhibition of DNA replication and transcription

They can also be purine/pyrimidine or folate antagonists (dihydrofolate reductase inhibitors-prevents nucleic acid formation)
This blocks DNA replication and transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give six examples of anti-metabolites.

A

Methotrexate- Folate
5-fluorouracil- Pyrimidine
6-mercaptopurine- Purine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

State some side effects of anti-metabolites.

A
  • Alopecia (not 5-fluorouracil),
  • Bone marrow suppression (–> anaemia, neutro/thrombocytopenia)
  • Increased risk of neutropenic sepsis,
  • Nausea/Vomiting, Mucositis/Diarrhoea, Fatigue,
  • Palmar-plantar erythrodysesthesia (PPE)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do anthracyclines work?

A

They intercalate into DNA or RNA sequences and inhibit transcription and replication

It also blocks DNA repair

They create DNA damaging and cell membrane damaging oxygen free radicals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give two examples of anthracyclines.

A

Doxorubicin

Epirubicin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

State some side effects of anthracyclines.

A 
Cardiac toxicity (probably due to the free radicals),  
Alopecia, 
Neutropenia, 
Nausea, Vomiting, Fatigue,  
Red urine (doxorubicin –‘the red devil’)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do vinca alkaloids and taxanes work?

A

Vinca alkaloids inhibit assembly of microtubules
Taxanes inhibit disassembly of microtubules
This forces the cells into mitotic arrest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

State some side effects of these drugs.

A

Nerve damage (peripheral neuropathy and autonomic neuropathy)
Hair loss
Nausea, Vomiting
Bone marrow suppression
Arthralgia (severe joint pain without swelling or signs of arthritis)
Allergy

19
Q

How do topoisomerase inhibitors work?

A

Topoisomerase is responsible for the unwinding of DNA and they induce temporary single and double strand breaks in the phosphodiester backbone

Topoisomerase inhibitors alter the binding of topoisomerase to DNA and allow permanent breaks in the DNA

20
Q

Give three examples of topoisomerase inhibitors.

A

Topotecan (topo 1)
Irinotecan (topo 1)
Etoposide (topo 2)

21
Q

State some side effects of topoisomerase inhibitors.

A

Irinotecan = acute cholinergic type syndrome (diarrhoea, abdominal cramps, diaphoresis – so they are given with atropine)
Hair loss
Nausea, Vomiting, Fatigue
Bone marrow suppression

22
Q

What are the six hallmarks of cancer?

A 
SPINAP 
Self-sufficient  
Pro-invasive and metastatic  
Insensitive to anti-growth signals  
Non-senescent
Anti-apoptotic  
Pro-angiogenic
23
Q

What are the four hallmarks of cancer that have recently been added?

A 
DIE U 
Dysregulated metabolism 
Inflammation 
Evades the immune system  
Unstable DNA
24
Q

Give three examples of receptors that are over-expressed in cancer.

A

EGFR – over-expressed in many breast and colorectal cancers

HER2 – breast

PDGFR – glioma (brain)

25
Q

Give an example of a ligand that is over-expressed in some cancers.

A

VEGF – prostate, kidney and breast cancer

26
Q

Give two examples of constitutive (ligand independent) receptor activation in cancer.

A

EGFR – lung cancer

FGFR – head and neck cancers, myeloma

27
Q

What do each of the following suffixes mean in relation to monoclonal antibodies:

a. -momab
b. -ximab
c. -zumab
d. -mumab

A

a.–momab
Derived from mouse antibodies

b.–ximab
Chimeric antibody

c.–zumab
Humanised antibody

d.–mumab
Fully human antibody

28
Q

Describe the structure of humanised monoclonal antibodies.

A

Murine (mouse) regions are interspersed within the with the light and heavy chains of the Fab portion

29
Q

Describe the structure of chimeric monoclonal antibodies.

A

The murine component of the variable region of the Fab section is maintained integrally

30
Q

What effect can monoclonal antibodies have on receptors and their activation?

A

They target the extracellular component of receptors and can prevent receptor dimerization, neutralise the ligand and cause internalisation of the receptor

NOTE: they also activate Fc-receptor-dependent phagocytosis or cytolysis induced complement-dependent cytotoxicity (CDC) or antibody-dependent cellular cytotoxicity (ADCC)

31
Q

Give two examples of monoclonal antibodies used in oncology.

A

Bevacizumab (avastin) – binds and neutralises VEGF

Cetuximab – targets EGFR

32
Q

How do small molecule inhibitors work?

A

They bind to the kinase domain of tyrosine kinase receptors within the cytoplasm and block autophosphorylation and downstream signalling

33
Q

What was the first targeted treatment for cancer and how did it work?

A

Glivec (imatinib) – it is a small molecule inhibitor that targets the ATP binding region within the kinase domain of BCR-ABL1

This inhibits the kinase activity of ABL1

34
Q

Give four examples of small molecule inhibitors that inhibit receptors.

A

Erlotinib (EGFR)
Gefitinib (EGFR)
Lapatinib (EGFR/HER2)
Sorafenib (VEGFR)

35
Q

Give three examples of small molecule inhibitors that inhibit intracellular kinases.

A

Sorafenib (Raf kinase) – this is in addition to its anti-VEGFR effects
Dasatinib (Src kinase)
Torcinibs (mTOR inhibitors)

36
Q

State some advantages and disadvantages of monoclonal antibodies.

A 
Advantages: 
 High target specificity 
 Cause ADCC, complement-mediated cytotoxicity and apoptosis induction 
 Can be radiolabelled
 Long half-life
 Good for haematological malignancies
Disadvantages: 
 Large and complex structure  
 Less useful against bulky tumours  
 Only useful against targets with extracellular domains  
 Not useful for constitutively activated tumours  
 Cause immunogenicity and allergy 
 IV administration  
 Expensive
37
Q

State some advantages and disadvantages of small molecule inhibitors.

A

Advantages:
 Can target tyrosine kinases without an extracellular domain or which are constitutively activated
 Pleiotropic targets (useful in heterogenic tumours/cross-talk)
 Oral administration
 Good tissue penetration
 Cheap
Disadvantages:
 Shorter half-life, more frequent administration
 Pleiotropic targets (more unexpected toxicity)

38
Q

State some resistance mechanisms to targeted therapies.

A

Mutations in ATP binding domain
Intrinsic resistance
Intragenic mutations
Upregulation of downstream signalling pathways

39
Q

Explain how anti-sense oligonucleotides work.

A

These are short single-stranded DNA-like molecules
They bind to the complementary sequence on mRNA and hinder its translation
It then recruits RNase H to cleave the target mRNA
Mechanism: anti-sense oligonucleotides

40
Q

Name a successful B-Raf inhibitor.

A

Vemurafenib

NOTE: side effects include arthralgia, skin rash and photosensitivity

41
Q

Explain how the PD-1 receptor-PDL1 ligand system works.

A

PD-1 receptor is on the cell membrane
When the ligand (PDL-1) binds to the PD-1 receptor, the body’s T cells can no longer recognise tumours as foreign
So blocking the PD-1 receptor will stimulate the immune system

42
Q

Name a drug that inhibiting PD-1.

A

Nivolumab (anti-PD1 antibody)

43
Q

what are the resistance mechanisms to cytotoxic chemo drugs

A

-DNA repair mechanism upregulated so DNA damage repaired – no double strand breaks
E.g. 6-mercaptopurine and irinotecan (topo 2)

-DNA adducts replaced via base-excision repair (using PARP)
E.g. Cyclophasphamide and Veliparib (BRCA)

-Drug effluxed from cell by ATP-binding cassette (ABC transporters)
E.g. Cisplatin or oxaliplatin (MRP1 gene)

CANKER - OBG (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions