cancer metabolism

Question 1

what are the cancer hallmarks

Answer 1

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

Question 2

what are the new cancer hallmarks

Answer 2

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

Question 3

what is the warbug effect

Answer 3

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.

Question 4

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

Answer 4

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

Question 5

what do normal cells prefer: anaerobic glycolysis or ox phos

Answer 5

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

Question 6

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

Answer 6

false it is like a dial

Question 7

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

Answer 7

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

Question 8

what are the signalling pathways that regulate cancer metabolism

Answer 8

-pi3k
-myc
-glucose
-glutamineaka myc

Question 9

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

Answer 9

glutamine metabolism

Question 10

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

Answer 10

glucose metabolism

Question 11

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

Answer 11

glucose to pyruvate to lactate

Question 12

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

Answer 12

glucose to pyruvate to lactate

Question 13

true or false: there is more glucose uptake in cancer

Answer 13

true

Question 14

bioenergic pathways varies accross cancer types: give examples

Answer 14

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

Question 15

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

Answer 15

true

Question 16

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

Answer 16

because then we can use that fact to treat cancer

Question 17

what does pemetrexed do

Answer 17

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

Question 18

what is pemetrexed

Answer 18

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

Question 19

what does cb839 do

Answer 19

blocks gls which converts glutamine to glutamate

Question 20

what is d 2 hydroxyglutarate q

Answer 20

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

Question 21

idh mutants reduces what

Answer 21

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

Question 22

how does idh mutants reduce dna accessibility

Answer 22

-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

Question 23

true or false: idh mutations are clinically targetable

Answer 23

true

Question 24

epigenetic remodeling relies on….

Answer 24

metabolites
like the ones made by glycolysis

Question 25

what does metabolomics do

Answer 25

- 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

Question 26

what does metabolomics integrate

Answer 26

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

Question 27

what are the 3 approaches to metabolomics

Answer 27

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

Question 28

tumor microenvironment contribute to metabolic ....

Answer 28

heterogeneity

Question 29

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

Answer 29

false it is macrophages and tregs

Question 30

when was tumor and diet association found

Answer 30

in 1914 by rous

Question 31

ptp1b deficiency enables what

Answer 31

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

Question 32

what happens when you get pten and ptpn1

Answer 32

you get way more cell proliferation and prostate cancer invasiveness

Question 33

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

Answer 33

false it is pi3k activation

Question 34

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

Answer 34

false it takes like 36 weeks

Question 35

high fat diet fuels prostate cancer progression by....

Answer 35

rewriting the metabolome and amplyfying the myc program

Question 36

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

Answer 36

true

Question 37

ionizing radiation causes what

Answer 37

replication independant double strand breaks that can kill non replicating cells

Question 38

what does nadoh do

Answer 38

redox contril and lipid biosynthesus

Question 39

what do nuclrotides do

Answer 39

nucleic acid synthesis and atp

Question 40

what does dietary methionine do with radiation

Answer 40

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

Question 41

what is fluoropyrimidine 5-fluorouracil (5-FU)

Answer 41

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

Question 42

5-FU exerts its anticancer effects through....

Answer 42

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

Question 43

Disruption of the one-carbon metabolism with methionine restriction create

Answer 43

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

Question 44

what does methotrexate do

Answer 44

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

Question 45

histidine catabolism is a major determinant of what

Answer 45

methotrexate sensitivity

Question 46

methotrexate and what majes the tumor skinnyyyyy

Answer 46

histidine

Question 47

The histidine degradation pathway markedly influences what:

Answer 47

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

Question 48

supression of insulin feedback enhances the efficacy of what

Answer 48

pi3k inhibitors

Question 49

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

Answer 49

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

Question 50

how does the checkpoint blockade work

Answer 50

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

Question 51

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

Answer 51

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

Question 52

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

Answer 52

true compared to control

Question 53

Obesity is a potential mediator of what?

Answer 53

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