Molecular pathology of cancer treatments

Question 1

Give a feature of normal chemotherapy and what this means for the pt

Answer 1

not selective for tumour cells, only targets cells which are dividing faster, so leads side effects

Question 2

List some side effects of conventional chemo

Answer 2

myelosuppression
hair loss
diarrhoea

Question 3

State three ways in which conventional chemo drugs work

Answer 3

1. binding to microtubules
2. inhibiting topoisomerase II (in DNA replication and transcription)
3. binding to DNA directly and inhibiting DNA synthesis by cross linking

Question 4

What type of tumour is conventional chemo good for?

Answer 4

fast dividing tumours

Question 5

Give examples of fast dividing tumours

Answer 5

acute leukaemia
germ cell tumours of testis 
lymphomas
embryonal paediatric tumours
choriocarcinoma

Question 6

Give a disadvantage other than side effects of conventional chemo

Answer 6

Not good for slow dividing tumours ie tumours that grow by lack of apoptosis and not by increased cell division

Question 7

What is the difference between targeted chemo and conventional?

Answer 7

can differentiate better between normal cells and cancer cells

Question 8

What are the advantages of targeted chemo?

Answer 8

1. more effective

2. less side effects

Question 9

What methods can we use to find the differences between cancers?

Answer 9

1. gene arrays
2. proteomics
3. tissue microarrays
4. immunohistochemistry

Question 10

List some cellular signalling problems that can lead to cancer formation

Answer 10

1. over-expression of growth factor receptors

2. continuous activation of growth factor receptors

Question 11

Give examples of treatments for cellular signalling problems in cancer

Answer 11

1. monoclonal antibodies to prevent growth factor binding extracelullarly
2. small molecular inhibitors which act intracellularly to prevent signal transduction inn receptors that are continuously on

Question 12

How does Cetuximab work?

Answer 12

humanised monoclonal chimeric IgG antibody against epidermal growth factor receptor (EGFR) that blocks the binding of EGF. The antibody binds competitively to EGFR. Prevents intracellular activation of tyrosine kinase

Question 13

How does herceptin work?

Answer 13

chimeric monoclonal antibody against extracellular Her 2 (human epidermal growth factor receptor 2). Prevents dimerisation of Her-2 AND causes endocytosis of the Her-2 and the antibody AND when lymphocytes bind there is cell cytotoxicity

Question 14

What is Her-2 associated with in cancer cells?

Answer 14

1. large size
2. high grade
3. aneuploidy (presence of abnormal number of chromosomes in a cell)
4. negative oestrogen receptor status
5. independent adverse prognostic factor

Question 15

How can we detect Her-2 amplification?

Answer 15

1. FISH - fluorescent in 2. situ hybridisation

immunohistochemistry

Question 16

What is Gleevec an example of?

Answer 16

A small molecular inhibitor

Question 17

How does Gleevec work?

Answer 17

It is a small molecular inhibitor of mutated c-kit which is continually active and leads to more transcription and more proliferation of the cells

Question 18

What does EGF do?

Answer 18

transcriptional upregulation leading to:

1. proliferation
2. angiogenesis
3. cell motility/invasion