Anticancer therapy (L22) Flashcards
solid tumours
when a lump of cancer cells form
develops from a single cancer cell to form a large cluster
what is chemotherapy?
use of chemicals to treat cancer
are associated with unpleasant side effects
what do we need to selectively kill?
infective organisms
our own abnormal cells
why is cancer cells being similar to normal cells a problem?
makes a challenge when trying to treat cancer
how do cancers develop?
mutations
some affect critical regulatory genes
most common mutations in genes that cause cancer
cell division
cell death
DNA stability
what do the mutations that cause cancer lead to?
uncontrolled growth of cells
aberrant survival of cells
genetic instability
what happens if theres evolution within the population of mutant cells?
faster growth
invasion of neighbouring tissue
spread to remote parts - metastasis
what is metastasis?
spread to remote parts
when do you need chemotherapy?
when you catch the cancer too late and it has metastasised
when surgery isn’t possible
cancer of the prostate gland
1 in 8 men in the UK will get prostate cancer
risk increases with age
cure rate is high if detected early
how does metastasis occur?
cells enter bloodstream and lymph nodes and then can easily travel round the body
2 categories of cancer chemotherapy
cytotoxic therapy - mostly by damaging DNA
targeted therapies - against a tumour-specific target
how are anti-cancer drugs developed?
chance observations
screening of natural products
rational drug design
targeted therapy
what does mustard gas do?
sulfur mustard - SCl2
potent drying agent that burns eyes, skin and respiratory tract
causes low blood counts
incredibly reactive
how is mustard gas used to treat cancer?
skin cancer
dripped it onto tumours and it had some effect
nitrogen mustard is now used instead as it is less reactive
examples of drugs causing damage to DNA
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
platinum based drugs
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
mode of discovery of cisplatin
chance observation using platinum electrodes
negatives of cisplatin
causes kidney and nerve damage
limitations of cytotoxic drugs
doses needed are close to the maximum acceptable doses
they are not very selective
small therapeutic window
cisplatin and carboplatin
carboplatin is the 2nd generation drug
same mechanism
fewer side effects
mode of discovery of carboplatin
screening a large number of related compounds
May Apple in cancer treatment
contain the drug etopodside - used in the treatment of cancers
podophyllum glycosides - useful anticancer activity
Daunorubicin in cancer treatment
found in Italy
roman tribe occupying area where soil sample was taken - red colour
looking for antibiotics - killed lots of cells so bad antibiotic
target of daunorubicin
targets topoisomerase which normally untangles DNA
• causes DNA to become tanged = catinated
leads to DNA damage and cell death
mode of discovery of daunorubicin
screening natural products
basis of selective killing
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
common side effects of cancer treatment
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
what are chemometics?
drugs that look like normal compounds but when incorporated in DNA stop cell division
guanine chemometic
6-thioguanine
used in treatment of childhood cancer - childhood leukaemia
hypoxanthine chemometic
6-mercaptopurine
childhood leukaemia
350 cases a year in the UK
peak at 3-4 yrs
acute lymphoblastic leukaemia (ALL) most common form
ALL treatment
treated with multiple drugs - 8
> 90% cure rate
treatment lasts 2-3 years
multiple toxicities
chronic myeloid leukaemia (CML) tumours
all carry a characteristic chromosome abnormality
• ‘Philadelphia translocation’
• chromosome 22 = Philadelphia chromosome
karyotype in CML
1 bigger chromosome 9 than normal
1 smaller chromosome 22 than normal
what happens in Philadelphia translocation?
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
what is imatinib?
developed by ‘Novartis’ to inhibit the abnormal BCR-AbL protein kinase
turns off phosphorylation
what is precision medicine?
by understanding the biology of the cancer we can develop new protocols and drugs to target specific abnormalities
