Exploiting tumour metabolism for patient benefit

Question 1

TF chemotherapy can cause metabolic changes.

Answer 1

true

Question 2

what can metabolic changes due to chemotherapy lead to?

Answer 2

drug induced resistance

Question 3

TF recurring tumours in patients will be the same as before

Answer 3

FALSE

Question 4

what is the biggest challenge to generalised therapy?

Answer 4

heterogenicity

Question 5

how can we see if a tumour is OP or glycolytic

Answer 5

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

Question 6

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

Answer 6

RTK inhibitors

Question 7

how will inhibition of the PI3K pathway target HEF1

Answer 7

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

Question 8

silibinin drug effects

Answer 8

stops glucose uptake
G1 cell cycle arrest
angiogenesis inhibition

Question 9

inhibiting hexokinases does what?

Answer 9

glycolysis inhibition

Question 10

drugs that target LDHA inhibit

Answer 10

lactate production

Question 11

drugs which target MCT1 inhibit?

Answer 11

transport of lactate across membranes

Question 12

how can we target cancers with unregulated respiration by OXPHOS

Answer 12

target the electron transport chain

Question 13

what can metformin do to the mitochondria and in cancer therapy

Answer 13

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

targets complex I in ETC

Question 14

What can atovaquone do to ATP

Answer 14

inhibit complex III so ATP cannot be generated

Question 15

other effects of metformin and atovaquone on tumours?

Answer 15

deoxygenate them
gives radiation therapy better effects
allevate hypoxia

Question 16

why is mutated IDH important in tumours?

Answer 16

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

mutation of IDH in many cancers

Question 17

mutation in IDH can do what?

Answer 17

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

Question 18

REDUCED DNA methylation _______ gene expression

Answer 18

increases

Question 19

what is ROS predominantly produced from?

Answer 19

mitochondrial activity

Question 20

TF is high levels of ROS always good for tumours?

Answer 20

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

Question 21

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

Answer 21

stop inhibiting degluttathione metabolism
OR
increase amount of hydrogen peroxide

these will overwhelm the antioxidant capacity and lead to apoptosis

Question 22

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

Answer 22

FA is needed for proliferating cells

Question 23

what does 2DG target?

Answer 23

hexokinases, hexokinases cant process 2GD so glycolysis cant continue

Question 24

how can statins be used as anticancer therapy

Answer 24

targets mevalonate pathway

Question 25

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

Answer 25

metformin +2DG
metformin+statins

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