Biological Basis of Cancer Chemotherapy Flashcards Preview

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Flashcards in Biological Basis of Cancer Chemotherapy Deck (51)
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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