cancer metabolism Flashcards

1
Q

what are the cancer hallmarks

A

-sustaining proliferative signaling
-evading growth supressors
-resisting cell death
-inducing angiogenesis
-enabling replicative immortality
-activating invasion and metastasis

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2
Q

what are the new cancer hallmarks

A

deregulating cellular energetics
-avoiding immune destruction
-tumor promoting inflammation
-genome instability and mutation

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3
Q

what is the warbug effect

A

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.

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4
Q

true or false: in cancer cells, they prefer aerobic glycolysis which makes less atp

A

true
-you make less atp made and more glycolytic intermediates and lactate

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5
Q

what do normal cells prefer: anaerobic glycolysis or ox phos

A

-ox phos when there is oxygen
-anaerobic glycolysis when there is no glycolysis

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6
Q

true or false: the relationship between glycolysis and oxphos is like a switch

A

false it is like a dial

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7
Q

true or false: there is more glycolysis when the tumor is progressing

A

false there is more oxphos when it progresses because there is less access to nutients and it is more acidic

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8
Q

what are the signalling pathways that regulate cancer metabolism

A

-pi3k
-myc
-glucose
-glutamineaka myc

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9
Q

in standard culture which is more common, glutamine metabolism or glucose metabolism

A

glutamine metabolism

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10
Q

in 3d culture which is more common: glucose or glutamine metabolism

A

glucose metabolism

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11
Q

in slice culture: which is more common: glucose or glutamine metabolism

A

glucose to pyruvate to lactate

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12
Q

in mouse culture: which is more common: glucose or glutamine metabolism

A

glucose to pyruvate to lactate

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13
Q

true or false: there is more glucose uptake in cancer

A

true

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14
Q

bioenergic pathways varies accross cancer types: give examples

A

prostate cancer do not rely much on glucose metabolism and fdg pet fails to image prostate tumors

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15
Q

true or false: high fat diet promotes aerobic glycolysis in prostate cancer

A

true

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16
Q

how can the fact that the diet can change the cancer metabolism be good

A

because then we can use that fact to treat cancer

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17
Q

what does pemetrexed do

A

blocks the cho-thf ro thf concersion in the folate cycle that is a part lf the purine synthesis

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18
Q

what is pemetrexed

A

it is ablocker ibn the purine biosynthesis
-it is supposed to look like folic acid to cock block

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19
Q

what does cb839 do

A

blocks gls which converts glutamine to glutamate

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20
Q

what is d 2 hydroxyglutarate q

A

it is made by mutant IDH and it is an onco metabolite which reduces demethylation by tet enzymes

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21
Q

idh mutants reduces what

A

dna demethylation which means that the dna is less accessible now since demethylation promotes dna access

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22
Q

how does idh mutants reduce dna accessibility

A

-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

23
Q

true or false: idh mutations are clinically targetable

A

true

24
Q

epigenetic remodeling relies on….

A

metabolites
like the ones made by glycolysis

25
Q

what does metabolomics do

A
  • 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
26
Q

what does metabolomics integrate

A

upstream genetic, transcriptomic and proteomic variatiln and exposome
-this is phenotype chracterization

27
Q

what are the 3 approaches to metabolomics

A

-static: global untargeted like lc-ms/ms
-dynamic: fluxomics
-imaging: ms based imaging like maldi-msi, ct or pet scan and raman spectroscopy

28
Q

tumor microenvironment contribute to metabolic ….

A

heterogeneity

29
Q

true or false: high fat diet promotes tumor associated interferon infiltration

A

false it is macrophages and tregs

30
Q

when was tumor and diet association found

A

in 1914 by rous

31
Q

ptp1b deficiency enables what

A

the ability of a high fat diet to drive the invasive character of pten deficient prostate cancers

32
Q

what happens when you get pten and ptpn1

A

you get way more cell proliferation and prostate cancer invasiveness

33
Q

true or false: tumors with pi3k deactivation are resistant to dietary restriction

A

false it is pi3k activation

34
Q

true or false: we see quicky the changes by genetic alterations that aggect the tumors response to diet

A

false it takes like 36 weeks

35
Q

high fat diet fuels prostate cancer progression by….

A

rewriting the metabolome and amplyfying the myc program

36
Q

true or false: duet and exercise makes the people getting tumor excision surgery recuperate better

A

true

37
Q

ionizing radiation causes what

A

replication independant double strand breaks that can kill non replicating cells

38
Q

what does nadoh do

A

redox contril and lipid biosynthesus

39
Q

what do nuclrotides do

A

nucleic acid synthesis and atp

40
Q

what does dietary methionine do with radiation

A

influences therapy in mouse cancer models and alters human metabolism
-basically the tumor shrinks

41
Q

what is fluoropyrimidine 5-fluorouracil (5-FU)

A

-is an antimetabolite drug that is widely used
for the treatment of cancer
-

42
Q

5-FU exerts its anticancer effects through….

A

inhibition of thymidylate synthase (TS) and
incorporation of its metabolites into RNA and DNA

43
Q

Disruption of the one-carbon metabolism
with methionine restriction create

A

redox and nucleotide metabolism vulnerabilities that can be exploited by administration of other therapies.

44
Q

what does methotrexate do

A

it inhibits the synthesis of dna, rna, thymidylates and proteins

45
Q

histidine catabolism is a major determinant of what

A

methotrexate sensitivity

46
Q

methotrexate and what majes the tumor skinnyyyyy

A

histidine

47
Q

The histidine degradation pathway markedly
influences what:

A

the sensitivity of cancer cells to methotrexate an may be exploited to improve methotrexate
efficacy through a simple dietary intervention

48
Q

supression of insulin feedback enhances the efficacy of what

A

pi3k inhibitors

49
Q

Therapeutic agents that target the PI3K pathway should be paired with strategies such as….

A

SGLT2 inhibition or the ketogenic diet to limit this self-defeating systemic feedback.

50
Q

how does the checkpoint blockade work

A

by releasinf a natural break on t cells so that they can recognize and attack the tumor

51
Q

paradoxal effects of obesity on t cell function during tumor progression and pd1 checkpoint blockade

A

-basically obesity makes the tumor bigger to control
-you get more pd1 and less ki67 cd8 T cells in obesity

52
Q

true or false: diet induced obesity makes tumor smaller when you have pd1 checkpoint blockade too

A

true compared to control

53
Q

Obesity is a potential mediator of what?

A

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

54
Q
A