Lecture 15: cancer 33 Flashcards
Identified tumour suppressor genes:
- Rb
- P53
- WT-1
- Ptc
- BRCA-1
- APC
Inherited cancer predisposition diseases
- Retinoblastoma
- Li Fraumeni
- Wilm’s tumour
- Gorlin’s syndrome
- Breast cancer
- Familial adenomatous polyposis coli (FAP)
Oncogenes vs tumour suppressor genes: number of alleles mutated to exert effect
oncogenes: one
TSG: 2
Oncogenes vs tumour suppressor genes: effect on the function of the protein
oncogene: Enhanced
TSG: reduced
Oncogenes vs tumour suppressor genes: inherited mutations:
oncogenes: RET, Abl
TSG: p53, RB, WT-1, Ptc, APC
Oncogenes:
activate, gain of function, dominant
TSG:
inactivating, loss of function, recessive
normal cell division, normal apoptosis:
HOMEOSTASIS
INCREASED cell division, normal apoptosis :
TUMOUR
Normal cell division, DECREASED apoptosis :
TUMOUR
cell cycle
G1 - growth 1
S - replicate genome
G2 - growth phase 2
M - cell division
Many genes control cell division:
- Many Genes Promote Cell Division
- Many Genes Block Cell Division
DNA detected by stable, active p53
- Hyperproliferative signals
- DNA damage
- Telomere shortening
- Hypoxia
outcome from p53 detecting DNA damage
- cell cycle arrest
- senescence
- apoptosis
p53 has been called the
‘guardian of the genome’
p53
• arrests cells when DNA is damaged
• turns on transcription of DNA repair genes and
genes that arrest cell cycle
• turns on apoptosis when all else fails
many cancers arise from defects in the machinery that regulates
cell growth and/or cell death
most cancer cells are defective in apoptotic response
⇑anti-apoptotic or
⇓ pro-apoptotic proteins
CANCER
Cancer cells have tricks to avoid apoptosis:
B-cell leukemias and lymphomas express
high levels of Bcl-2
Cancer cells have tricks to avoid apoptosis: Lung and colon cancer cells
secrete
“decoy” molecules that bind and inactivate MHC type1 receptors
⇓T cell recognition sites
—Cytotoxic T-lymphocytes & NK cannot kill the cancer cells
routes of tumour spread
- direct
- via lymphatics
- transcoelomic
- field change
- via bloodtsream
Metastasis mechanism
still poorly understood
metastasis is promoted by
- ⇓ adherence between cells
- Synthesis of defective basement membrane
- Tumour angiogenesis
- ⇑cell motility
- Secrete growth factors
- Secrete alternative extracellular matrix
- Secrete proteinases
- Evade host immune system
treatment for cancer:
- Surgery
- Radiotherapy
- -Chemotherapy
- Endocrine-related treatments
- Immunotherapy
- –Interferons, vaccination
- Molecular mechanism-based
an effective screening should be
-Be affordable to the healthcare system
–Be acceptable to all social groups
-Have good discrimination between benign & malignant
lesions
-Show a reduction in mortality from the cancer
Herceptin as mode of action
=monoclonal antibody binds to erbB2 receptor sites
Inhibits receptor function
1.Cell cycle arrest
blocks cell cycle in G1
- Suppresses angiogenesis
⇑antiangiogenic factors
⇓proangiogenic factors
cancer is a ___ of diseases
group
cancer is controlled / uncontrolled cell division
uncontrolled
- aberrant differentiation & cell interactions
2 types of tumours:
benign & malignant
cancer affects
a large proportion of the population (but is rare from the cells perspective)
Many carcinogens act as
mutagens - cancer not usually become apparent until years after exposure
_____ in cellular function need to occur before a cell can become malignant
MULTIPLE CHANGEs
include defects in the machinery that regulates cell growth and death
Gain of function mutations occur in
oncogenes
loss of function mutations associated with
tumour suppressors
many cancers display
genomic instability
cancer may arise from
‘stem cells’
__ treatments are availble
variable
- often used in combination
New insights into tumour biology is providing
new therapies
