Biological Basis of Cancer Chemotherapy Flashcards Preview

SSC- Biology of Cancer > Biological Basis of Cancer Chemotherapy > Flashcards

Flashcards in Biological Basis of Cancer Chemotherapy Deck (51)
1

What are the potential ways that tumours can spread? 

  • Local
  • Lymphatics
  • Blood
  • Implantation 

 

2

What is local spread of cancer? 

Direct involvement of surrounding structures 

3

What cancers spread via the lymphatics? 

  • Carcinomas 
  • Melanomas

 

4

What cancers spread via the blood? 

  • Sarcomas
  • Later stage carcinomas

 

5

What happens in implantation spread of cancer? 

There is mechanical spread of detatched clumps of tumour cells to the peritoneum, ureters, or CSF 

6

What are the treatment options for cancer? 

  • Surgery
  • Radiotherapy
  • Chemotherapy
  • Hormones
  • Biologically targetted therapy 

 

7

In what ways can chemotherapy be used in treating cancer? 

  • Radical primary treatment
  • Adjuvant therapy
  • Neoadjuvant therapy
  • Palliative care in advanced disease

 

8

Where is chemotherapy used as a radical primary treatment? 

In haemotological malignancies, such as lymphomas and leukaemias 

9

What is the definition of adjuvant chemotherapy? 

Post-operative treatment in a patient at high risk of microscopic metastases after the removal of the primary tumour 

10

What is neoadjuvant chemotherapy? 

Primary treatment of patients with clinically localised tumour - use chemotherapy upfront to improve the outcome of the primary therapy

11

What are the advantages of neoadjuvant chemotherapy? 

  • Can assess the biological responsiveness of the tumour
  • May allow for conservation surgery
  • May achieve pCR (pathological complete response 

 

12

What determines the rate of tumour growth? 

  • Growth fraction
  • Duration of cell cycle
  • Rate of cell loss

13

What does topoisomerase 1 do? 

It causes transient single strand cleavage, relaxes the strand, and then sticks it back together 

14

How does topoisomerase 1 inhibition work? 

You get binding to the TOPO 1-DNA complex, without affecting the cleavage region. This means that the enzyme cannot rejoin the DNA, resulting in a double stranded break and therefore cell apoptosis 

15

What is the advantage of a unique tumour-activated agent? 

It wouldn't affect normal tissue, and so minimises side effects

16

Give an example of a tumour activated chemotherapy agent? 

Xeloda 

17

What is the mechanism of action of xeloda? 

  1. It is absorbed in the intestine
  2. It is converted to 5'-DFCR CyD and then 5'-DFUR 
  3. 5'-DFCR CyD and 5'-DFUR are transported into the tumour tissue, where they are converted to 5-FU 
  4. 5-FU blocks DNA replication

 

18

What happens to spindle microtubules once chromosomes are aligned at the metaphase plate? 

They depolymerise, moving sister chromatids towards opposite poles 

19

How do micro-tubule binding agents affect microtubule dynamics? 

  • Inhibit polymerisation
  • Stimulate polymerisation and prevent depolymerisation 

 

20

What does it need to be ensured if combination therapy is to improve activity? 

  • Drugs have a different mechanism of action 
  • Drugs have different mechanisms of resistance

 

21

What needs to be ensured if combination therapy is to be safe? 

They have compatible side effects

22

What is P-glycoprotein? 

An ATP-powered efflux pump 

23

What does P-glycoprotein do? 

Pumps cytotoxic agents out of the cells against the concentration gradient 

24

What repair pathway is employed in single-stand breaks? 

Base excision repair 

25

What enzyme is used in base excision repair? 

PARP 

26

What repair pathway is employed in double stranded DNA breaks? 

Recombinational repair 

27

What enzymes are used in recombinational repair? 

  • ATM in homologous recombination repair 
  • DNA-PK in non-homologous end joining 

 

28

What repair pathway is employed when bulky adducts are added to DNA? 

Nucleotide-excision repair

29

What enzymes are used in nucleotide-excision repair? 

  • XP
  • Polymerases

 

30

What repair pathway is employed with insertions and deletions to DNA? 

  • MSH2
  • MLH1

 

31

What repair pathway is employed with O6-alkylguanine DNA damage? 

Direct reversal

32

What enzyme is involved in direct reversal of O6-alkylguanine mutations? 

AGT

33

Give the process of repair of single strand DNA breaks by PARP-1

  1. PARP binds directly to single strand breaks
  2. Once bound to damaged DNA, PARP modifies itself producing large branches chains or PAR
  3. PAR recruits repair enzymes, which fix the break
  4. PAR chains are degraded via PARG

 

34

What effect does inhibiting PARP-1 have on DNA? 

It increases double stranded DNA breaks, as it prevents recruitment of repair factors to repair SSB, which then progress to DSB after S-phase of DNA replication

35

Give an example of a homologous recombination repair deficient cell

Cells with BRCA 1 or 2 mutations 

36

How does olaparib work in BRCA-deficient cancer cells? 

It causes double strand breaks, which can be repaired effectively by HR pathways in normal cells, allowing them to survive, but kills cancer cells as they don't have the pathway to repair 

37

Give two examples of hormones that can be carcinogenic

  • Oestrogen in breast cancer
  • Testosterone in prostate cancer 

 

38

What is important when considering carcinogenic hormones? 

Prolonged exposure, e.g. in the case of breast cancer, should consider age of menarche, age of first pregnancy etc 

39

What are the categories of endocrine therapies for breast cancer? 

  • Anti-oestrogens
  • Aromatase inhibitors
  • Progestogens
  • LHRH agonists

40

Give an example of an anti-oestrogen breat cancer therapy 

Tamoxifen

41

Give 5 examples of aromatase inhibitors

  • Anastrazole
  • Letrozole
  • Exemestane
  • Vorozole
  • Formestane

 

42

Where do aromatase inhibitors have a particular use? 

When women are post menopausal 

43

Why do aromatase inhibitors have a particular role when women are post-menopausal? 

Because they are reliant on the aromatase enzyme to produce any oestrogen

Doesn't work in pre-menopausal women, as they are producing their own ovarian oestrogen

 

 

44

Give an example of a progtesterone therapy for breast cancer

Megestrol 

45

Give an example of a LHRH agonist 

Goserelin

46

What are the categories of endocrine therapies for prostate cancer? 

LHRH agonists

Anti-androgens

Oestrogen

Castration 

 

 

47

Give 3 examples of anti-androgens

  • Cytoproterone acetate
  • Flutamide
  • Bicalutamide

 

 

48

Give an example of an oestrogen therapy for prostate cancer

Stilboestrol

49

How does giving oestrogen help in prostate cancer? 

It compensates for the testosterone drive for prostate cancer 

50

Give an example of a novel endocrine agent used in the treatment of prostate cancer

Abiraterone 

51

What is the mechanism of action of abiraterone? 

It inhibits the crucial CYP17A1 enzyme, which is needed for the conversion of pregnenolone and progesterone to testosterone