Exploiting tumour metabolism for patient benefit Flashcards Preview

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Flashcards in Exploiting tumour metabolism for patient benefit Deck (25)
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1
Q

TF chemotherapy can cause metabolic changes.

A

true

2
Q

what can metabolic changes due to chemotherapy lead to?

A

drug induced resistance

3
Q

TF recurring tumours in patients will be the same as before

A

FALSE

4
Q

what is the biggest challenge to generalised therapy?

A

heterogenicity

5
Q

how can we see if a tumour is OP or glycolytic

A

radiolabel lactate and pyruvate and use tracer to ID how they’re being used in cells

6
Q

what can you target alongside the PI3K pathway to have a more effective tumour response to therapy

A

RTK inhibitors

7
Q

how will inhibition of the PI3K pathway target HEF1

A

can stop its stabilisation which is induced by the PI3K pathway independent of available oxygen

8
Q

silibinin drug effects

A

stops glucose uptake
G1 cell cycle arrest
angiogenesis inhibition

9
Q

inhibiting hexokinases does what?

A

glycolysis inhibition

10
Q

drugs that target LDHA inhibit

A

lactate production

11
Q

drugs which target MCT1 inhibit?

A

transport of lactate across membranes

12
Q

how can we target cancers with unregulated respiration by OXPHOS

A

target the electron transport chain

13
Q

what can metformin do to the mitochondria and in cancer therapy

A

inhibits complex 1 so metabolites cant go through the etc and generate ATP

targets complex I in ETC

14
Q

What can atovaquone do to ATP

A

inhibit complex III so ATP cannot be generated

15
Q

other effects of metformin and atovaquone on tumours?

A

deoxygenate them
gives radiation therapy better effects
allevate hypoxia

16
Q

why is mutated IDH important in tumours?

A

normally: conversion of isocitrate to a-KG which changes DNA methylation which then alters gene regulation

mutation of IDH in many cancers

17
Q

mutation in IDH can do what?

A

change a-KG to 2HG. this accumulation of 2HG reduced DNA methylation which increases gene expression= good for cancer

18
Q

REDUCED DNA methylation _______ gene expression

A

increases

19
Q

what is ROS predominantly produced from?

A

mitochondrial activity

20
Q

TF is high levels of ROS always good for tumours?

A

no, initially increase proliferation. but if it goes over a toxic threshold the anti-oxidant capacity is overwhelmed and it leads to apoptosis

21
Q

how can we use ROS as a anticancer therapy? 2 ways

A

stop inhibiting degluttathione metabolism
OR
increase amount of hydrogen peroxide

these will overwhelm the antioxidant capacity and lead to apoptosis

22
Q

why can inhibiting FA synthesis be used as an anti cancer therapy?

A

FA is needed for proliferating cells

23
Q

what does 2DG target?

A

hexokinases, hexokinases cant process 2GD so glycolysis cant continue

24
Q

how can statins be used as anticancer therapy

A

targets mevalonate pathway

25
Q

why is combination therapy Better? example of combination therapy here?

A

metformin +2DG
metformin+statins

combination is goo as tumours always adapt, combination covers more areas