T9: Cancer Flashcards
Cancer
diseases characterized by uncontrolled growth and spread of abnormal cells
very common
tumours
aka neoplasms
abnormal mass of cells
benign (local) or malignant (invade)
Hallmarks of cancer
- self sufficiency of cells in signals controlling growth
- Loss of sensitivity to antigrowth signals
- Evasion of apoptosis
- Development of limitless replicative potential
- Angiogenesis
- Tissue invasion and metastasis
elephants have 20 copies of
TP53
bodily mechanisms against cancer
- apoptosis when uncontrolled cell div. occurs
- ## Immune (T) cells recognize and destroy cells that div. at bad times
stem cells
all over body
replace warn out cells
bad : can reproduce & differentiate (pre-adapted for cancer)
specialized tissues : placenta
placental stem cells invade maternal uterine wall
suppresses maternal immune response by recruiting t-cells
Trade-offs in cancer
- stem cells
- specialized tissues (placental)
- growth (paths for rapid cell div.)
most cancers occur
late in life
childhood cancers
bone, brain
… Tissues that have undergone rapid evolution for larger size or other modification in recent evolutionary past
‘cancer driver’ genes
promote cancer
persist due to other fitness benefits
(trade-off hypothesis)
Why cancer? Why variation in cancer?
- trade-offs
- mismatch
- selection shadow (inefficient selection to improve defences late in life)
mismatch in cancer
- diet, lifestyle
- reproduction
- humans now live longer
selection shadow
when do most cancers occur
late in life due to time needed for mutation accumulation
genetic variation in a tumour
= more resistant
more likely to have treatment resistant cells
= more likely reoccurrence
cancerous cell growth within individuals
favoured by NS
-mutations allow for outcompeting
-ingredients for evolution are present: genetic variation (esp. because of huge pop. size),
proof immune system does a good job
autopsies of ppl that did not die of cancer show tons of neoplasms
Chemotherapy
stops all cell replication
- leads to resistance
adaptive therapy
-lower dose chemo
-control tumour size, keep less aggressive clones alive
treatment: target public goods
cancer cells produce PGs that suppress immune system, and stimulate angiogenesis
cheaters
benefit off public goods w/out paying cost
finding a treatment that yields evolution proof results
Need to understand selection on cancer cells in their natural environment
Need measures of fitness of cancer cells with different phenotypes
cancer as asexual cell reproduction
mitosis (making copies)
mutations
sometimes advantageous - spread clonally
