Anticancer therapy (L22)

Question 1

solid tumours

Answer 1

when a lump of cancer cells form

develops from a single cancer cell to form a large cluster

Question 2

what is chemotherapy?

Answer 2

use of chemicals to treat cancer

are associated with unpleasant side effects

Question 3

what do we need to selectively kill?

Answer 3

infective organisms

our own abnormal cells

Question 4

why is cancer cells being similar to normal cells a problem?

Answer 4

makes a challenge when trying to treat cancer

Question 5

how do cancers develop?

Answer 5

mutations

some affect critical regulatory genes

Question 6

most common mutations in genes that cause cancer

Answer 6

cell division

cell death

DNA stability

Question 7

what do the mutations that cause cancer lead to?

Answer 7

uncontrolled growth of cells

aberrant survival of cells

genetic instability

Question 8

what happens if theres evolution within the population of mutant cells?

Answer 8

faster growth

invasion of neighbouring tissue

spread to remote parts - metastasis

Question 9

what is metastasis?

Answer 9

spread to remote parts

Question 10

when do you need chemotherapy?

Answer 10

when you catch the cancer too late and it has metastasised

when surgery isn’t possible

Question 11

cancer of the prostate gland

Answer 11

1 in 8 men in the UK will get prostate cancer

risk increases with age

cure rate is high if detected early

Question 12

how does metastasis occur?

Answer 12

cells enter bloodstream and lymph nodes and then can easily travel round the body

Question 13

2 categories of cancer chemotherapy

Answer 13

cytotoxic therapy - mostly by damaging DNA

targeted therapies - against a tumour-specific target

Question 14

how are anti-cancer drugs developed?

Answer 14

chance observations

screening of natural products

rational drug design

targeted therapy

Question 15

what does mustard gas do?

Answer 15

sulfur mustard - SCl2

potent drying agent that burns eyes, skin and respiratory tract

causes low blood counts

incredibly reactive

Question 16

how is mustard gas used to treat cancer?

Answer 16

skin cancer

dripped it onto tumours and it had some effect

nitrogen mustard is now used instead as it is less reactive

Question 17

examples of drugs causing damage to DNA

Answer 17

drugs that chemically react with DNA
• carboplatin - treatment of ovarian cancer

drugs that block formation of DNA
• take away the bases needed for the strands t grow

drugs that cause an enzyme to covalently bind to DNA
• doxorubicin

Question 18

platinum based drugs

Answer 18

e.g. carboplatin

cisplatin is the mother of them all

very effective for certain cancers

Cl’s bind to DNA and stop it replicating, stopping cancer cells multiplying

Question 19

mode of discovery of cisplatin

Answer 19

chance observation using platinum electrodes

Question 20

negatives of cisplatin

Answer 20

causes kidney and nerve damage

Question 21

limitations of cytotoxic drugs

Answer 21

doses needed are close to the maximum acceptable doses

they are not very selective

small therapeutic window

Question 22

cisplatin and carboplatin

Answer 22

carboplatin is the 2nd generation drug

same mechanism

fewer side effects

Question 23

mode of discovery of carboplatin

Answer 23

screening a large number of related compounds

Question 24

May Apple in cancer treatment

Answer 24

contain the drug etopodside - used in the treatment of cancers

podophyllum glycosides - useful anticancer activity

Question 25

Daunorubicin in cancer treatment

Answer 25

found in Italy

roman tribe occupying area where soil sample was taken - red colour

looking for antibiotics - killed lots of cells so bad antibiotic

Question 26

target of daunorubicin

Answer 26

targets topoisomerase which normally untangles DNA
• causes DNA to become tanged = catinated

leads to DNA damage and cell death

Question 27

mode of discovery of daunorubicin

Answer 27

screening natural products

Question 28

basis of selective killing

Answer 28

some cancers consist of cels that are slightly more sensitive to DNA damage than normal cells

depends on the fact that most cancers divide faster than normal cells

Question 29

common side effects of cancer treatment

Answer 29

diarrhoea
sore mouth
hair loss

drugs are not specific
e.g. gastrointestinal cells are also rapidly dividing tissues so are also targeted by the cancer cells

Question 30

what are chemometics?

Answer 30

drugs that look like normal compounds but when incorporated in DNA stop cell division

Question 31

guanine chemometic

Answer 31

6-thioguanine

used in treatment of childhood cancer - childhood leukaemia

Question 32

hypoxanthine chemometic

Answer 32

6-mercaptopurine

Question 33

childhood leukaemia

Answer 33

350 cases a year in the UK

peak at 3-4 yrs

acute lymphoblastic leukaemia (ALL) most common form

Question 34

ALL treatment

Answer 34

treated with multiple drugs - 8

> 90% cure rate

treatment lasts 2-3 years

multiple toxicities

Question 35

chronic myeloid leukaemia (CML) tumours

Answer 35

all carry a characteristic chromosome abnormality
• ‘Philadelphia translocation’
• chromosome 22 = Philadelphia chromosome

Question 36

karyotype in CML

Answer 36

1 bigger chromosome 9 than normal

1 smaller chromosome 22 than normal

Question 37

what happens in Philadelphia translocation?

Answer 37

parts of 2 different genes are fused together - BCR and AbI

forms BCR-AbL - new protein thats a highly activate tyrosine kinase
• abnormal protein switches on cell division by activating other proteins by phosphorylation

Question 38

what is imatinib?

Answer 38

developed by ‘Novartis’ to inhibit the abnormal BCR-AbL protein kinase

turns off phosphorylation

Question 39

what is precision medicine?

Answer 39

by understanding the biology of the cancer we can develop new protocols and drugs to target specific abnormalities