Hallmarks of Cancer 1,2,3 Flashcards
normal cell division is _____
controlled
cancer is a ______ process
multistep
what do cancer cells develop characteristics to do?
move from the primary mass to around the body- metastasise
what types of cancer are the hardest to treat? why?
metastasis- aggressive and hard to control
most common cancer in men? women?
men- prostate
women- breast
6 hallmarks of cancer?
1: self sufficiency in proliferative growth signals
2: insensitive to growth inhibitory signals
3: evasion of apoptosis
4: limitless replicative potent;l
5: induction of angiogenesis
6: induction of metastasis
TME is highly ________. meaning?
interconnected
cross talk between lots of cells
examples of non cancer cells in the ME?
endothelial cells
fibroblasts
immune cells
what enables communication in the TME?
CYTOKINES
growth factors
what is the role of non-cellular solid material in the TME?
structure and support
TF: the tumour ME is hypoxic? explain? what does this lead to?
yes, depravation of oxygen. leads to differences in cell characteristic
what pH is the TME?
acidic
what types of inflammation exist in the TME?
pro and anti tumour inflammation
TF: immune cells have help tumour cells evade immune surveillance?
TRUE
what do IDO positive dendritic cells do?
suppress T-cell function and anti-cancer immune response
4 additional hallmarks of cancer?
evading immune destruction
reprogramming energy metabolism to pro tumour
tumour promoting inflammation
genome instability and mutation
5 steps of cancer from normal to metastatic
normal hyperplasia (normal cells in excess carcinoma in situ (localised) invasive cancer (surrounding tissue) metastatic cancer
what is a carcinoma?
cancer associated changes but staying local
what happens to the cells at the cancer differentiated stage?
cells still resemble normal cells.
what is dedifferentiation in cancer?
cells differentiate but in cancer the reverse happens so they no longer resemble the tissue
what underpins dedifferenciation?
DNA changes-
what are epigenetic changes?
changes that influence gene expression
switch genes on and off
are epigenetic changes mutations?
NO
just changes transcription level
3 gene classes involved in cancer development
oncogenes
TSGs
modifying genes
role of oncogenes
GO signal- gain in function
TF: oncogenes are recessive
false, mainly dominant
what are protooncogenes
normal genes that mutate to form oncogenes
TSGs role
loss of function, STOP signal
TSGs are dominant or recessive?
recessive
are modifying genes a gain or loss in function?
either
phenotypic hallmarks of cancer
increased proliferation
inappropriate survival/ no apoptosis
immortalisation
invasion, angiogenesis and metastatis
TF: most cancers are familial
FALSE most are sporadic
TF: the mutations seen in familial cancers are often the same as in sporadic cancers
true
why are you more likely to get cancer if you have it in your family?
familial cancer mutations in one allele that’s inherited.
therefore you only need one more mutation to get cancer
in sporadic you need 2 random mutations
signs of retinoblastoma
white pupil
squint inflamed eye
enlarged pupil
if retinoblastoma is inherited how many eyes does it tend to effect vs sporadic
onset if familial vs sporadic
both eyes, mutation is in every cell in the body. tends to occur earlier in life
so why is sporadic retinoblastoma rare?
you need two random events to occur simultaneously in the same cell. in familial you only need one in any cell as they all possess the single mutant allele
what phase of the cell cycle can apoptosis occur?
G1
can stop and go into a inhibited phase
what protein is important in regulating the transition between G1 and S
pRb
effect of pRB on G1–> S transition? effect?
inhibits
stops proliferation
what does phosphorylation of pRb do?
can no longer bind to E2F. E2F switches on genes which enable G1-S transition
therefore phosphorylation. leads to proliferation
how else can pRb be taken away from binding E2F?
bound to viral proteins
cells which mutate in colon cancer?
APC MLH1 and MSH2 N-CAM K-ras p53
APC change in colon cancer? function of this gene?
LOSS
cell adhesion
cell proliferation
K-ras change in colon cancer? gene function?
GAIN
oncogene
N-CAM change in colon cancer? gene function?
loss
cell adhesion
p-53 change in colon cancer? gene function?
LOSS
DNA damage réponse, apoptosis
MSH2 MLH1 change in colon cancer? gene function?
loss
DNA repair
APC in normal cells?
in a complex
consequently there’s a degradation of proteins e.g. beta catenin
keeps a check on function
APC in tumour cells?
cant bind in its complex, meaning B-catenin and other proteins start to function
results in gene transcription changes towards metastatic state
TF: K-ras doesn’t work by signal transduction
false- it does
receptors on surface which respond to signals outside the cells
2 pathways off the TK receptor?
MAPK
PI3K-AKT
MAPK and PI3K pathways are drivers of?
proliferation
PTEN effects on PI3K
PTEN is a TSG which puts the breaks on PI3K
effects of K-RAS changes?
mutated becomes hyperactivated- drives MAPK pathway irrespective of TK receptor ligand binding on outside of cell
proliferation
p53 has an active response to?
DNA damage
what 2 things do p53 do after DNA damage?
- stop transition from G1-S phase- allows time for DNA repair
- apoptosis activation
p53 is lost in ____% of tumours
50
the rate of genomic instability and DNA repair deficiencies ______ during carcinogenesis
INCREASES
What is mismatch repair? what can mutations do to this?
which genes does this involve?
removes incorrectly matched base pairs in the new strand of DNA upon replication
mutations: loss of function of mismatch repair proteins
MSH2 and MLH1
