cancer metabolism Flashcards
what are the cancer hallmarks
-sustaining proliferative signaling
-evading growth supressors
-resisting cell death
-inducing angiogenesis
-enabling replicative immortality
-activating invasion and metastasis
what are the new cancer hallmarks
deregulating cellular energetics
-avoiding immune destruction
-tumor promoting inflammation
-genome instability and mutation
what is the warbug effect
The Warburg Effect is a phenomenon in cancer cells where they preferentially use glycolysis (a less efficient way of generating energy) even in the presence of oxygen. Named after Otto Warburg, this metabolic shift supports rapid cell growth and is a characteristic feature of many cancer types.
true or false: in cancer cells, they prefer aerobic glycolysis which makes less atp
true
-you make less atp made and more glycolytic intermediates and lactate
what do normal cells prefer: anaerobic glycolysis or ox phos
-ox phos when there is oxygen
-anaerobic glycolysis when there is no glycolysis
true or false: the relationship between glycolysis and oxphos is like a switch
false it is like a dial
true or false: there is more glycolysis when the tumor is progressing
false there is more oxphos when it progresses because there is less access to nutients and it is more acidic
what are the signalling pathways that regulate cancer metabolism
-pi3k
-myc
-glucose
-glutamineaka myc
in standard culture which is more common, glutamine metabolism or glucose metabolism
glutamine metabolism
in 3d culture which is more common: glucose or glutamine metabolism
glucose metabolism
in slice culture: which is more common: glucose or glutamine metabolism
glucose to pyruvate to lactate
in mouse culture: which is more common: glucose or glutamine metabolism
glucose to pyruvate to lactate
true or false: there is more glucose uptake in cancer
true
bioenergic pathways varies accross cancer types: give examples
prostate cancer do not rely much on glucose metabolism and fdg pet fails to image prostate tumors
true or false: high fat diet promotes aerobic glycolysis in prostate cancer
true
how can the fact that the diet can change the cancer metabolism be good
because then we can use that fact to treat cancer
what does pemetrexed do
blocks the cho-thf ro thf concersion in the folate cycle that is a part lf the purine synthesis
what is pemetrexed
it is ablocker ibn the purine biosynthesis
-it is supposed to look like folic acid to cock block
what does cb839 do
blocks gls which converts glutamine to glutamate
what is d 2 hydroxyglutarate q
it is made by mutant IDH and it is an onco metabolite which reduces demethylation by tet enzymes
idh mutants reduces what
dna demethylation which means that the dna is less accessible now since demethylation promotes dna access
how does idh mutants reduce dna accessibility
-the ctcf can’t bind anymore to dna so it can’t create the tad domains to seperate the 2 genes
-so now it just makes a big tad domains
true or false: idh mutations are clinically targetable
true
epigenetic remodeling relies on….
metabolites
like the ones made by glycolysis
what does metabolomics do
- Measures and interprets changes in the metabolome, the entire repertoire of
small molecules (MW<1500Da) in biofluids, cells, tissues, organisms
-provides funtional infomation aka what is happening
what does metabolomics integrate
upstream genetic, transcriptomic and proteomic variatiln and exposome
-this is phenotype chracterization
what are the 3 approaches to metabolomics
-static: global untargeted like lc-ms/ms
-dynamic: fluxomics
-imaging: ms based imaging like maldi-msi, ct or pet scan and raman spectroscopy
tumor microenvironment contribute to metabolic ….
heterogeneity
true or false: high fat diet promotes tumor associated interferon infiltration
false it is macrophages and tregs
when was tumor and diet association found
in 1914 by rous
ptp1b deficiency enables what
the ability of a high fat diet to drive the invasive character of pten deficient prostate cancers
what happens when you get pten and ptpn1
you get way more cell proliferation and prostate cancer invasiveness
true or false: tumors with pi3k deactivation are resistant to dietary restriction
false it is pi3k activation
true or false: we see quicky the changes by genetic alterations that aggect the tumors response to diet
false it takes like 36 weeks
high fat diet fuels prostate cancer progression by….
rewriting the metabolome and amplyfying the myc program
true or false: duet and exercise makes the people getting tumor excision surgery recuperate better
true
ionizing radiation causes what
replication independant double strand breaks that can kill non replicating cells
what does nadoh do
redox contril and lipid biosynthesus
what do nuclrotides do
nucleic acid synthesis and atp
what does dietary methionine do with radiation
influences therapy in mouse cancer models and alters human metabolism
-basically the tumor shrinks
what is fluoropyrimidine 5-fluorouracil (5-FU)
-is an antimetabolite drug that is widely used
for the treatment of cancer
-
5-FU exerts its anticancer effects through….
inhibition of thymidylate synthase (TS) and
incorporation of its metabolites into RNA and DNA
Disruption of the one-carbon metabolism
with methionine restriction create
redox and nucleotide metabolism vulnerabilities that can be exploited by administration of other therapies.
what does methotrexate do
it inhibits the synthesis of dna, rna, thymidylates and proteins
histidine catabolism is a major determinant of what
methotrexate sensitivity
methotrexate and what majes the tumor skinnyyyyy
histidine
The histidine degradation pathway markedly
influences what:
the sensitivity of cancer cells to methotrexate an may be exploited to improve methotrexate
efficacy through a simple dietary intervention
supression of insulin feedback enhances the efficacy of what
pi3k inhibitors
Therapeutic agents that target the PI3K pathway should be paired with strategies such as….
SGLT2 inhibition or the ketogenic diet to limit this self-defeating systemic feedback.
how does the checkpoint blockade work
by releasinf a natural break on t cells so that they can recognize and attack the tumor
paradoxal effects of obesity on t cell function during tumor progression and pd1 checkpoint blockade
-basically obesity makes the tumor bigger to control
-you get more pd1 and less ki67 cd8 T cells in obesity
true or false: diet induced obesity makes tumor smaller when you have pd1 checkpoint blockade too
true compared to control
Obesity is a potential mediator of what?
immune dysfunction and tumor progression that can be successfully reversed by PD-(L)1 checkpoint inhibition resulting in heightened efficacy.
-when you are fatter in colorectal cancers if you have checkpoint blockade you survive more
