Exploiting tumour metabolism for patient benefit Flashcards
TF chemotherapy can cause metabolic changes.
true
what can metabolic changes due to chemotherapy lead to?
drug induced resistance
TF recurring tumours in patients will be the same as before
FALSE
what is the biggest challenge to generalised therapy?
heterogenicity
how can we see if a tumour is OP or glycolytic
radiolabel lactate and pyruvate and use tracer to ID how they’re being used in cells
what can you target alongside the PI3K pathway to have a more effective tumour response to therapy
RTK inhibitors
how will inhibition of the PI3K pathway target HEF1
can stop its stabilisation which is induced by the PI3K pathway independent of available oxygen
silibinin drug effects
stops glucose uptake
G1 cell cycle arrest
angiogenesis inhibition
inhibiting hexokinases does what?
glycolysis inhibition
drugs that target LDHA inhibit
lactate production
drugs which target MCT1 inhibit?
transport of lactate across membranes
how can we target cancers with unregulated respiration by OXPHOS
target the electron transport chain
what can metformin do to the mitochondria and in cancer therapy
inhibits complex 1 so metabolites cant go through the etc and generate ATP
targets complex I in ETC
What can atovaquone do to ATP
inhibit complex III so ATP cannot be generated
other effects of metformin and atovaquone on tumours?
deoxygenate them
gives radiation therapy better effects
allevate hypoxia
why is mutated IDH important in tumours?
normally: conversion of isocitrate to a-KG which changes DNA methylation which then alters gene regulation
mutation of IDH in many cancers
mutation in IDH can do what?
change a-KG to 2HG. this accumulation of 2HG reduced DNA methylation which increases gene expression= good for cancer
REDUCED DNA methylation _______ gene expression
increases
what is ROS predominantly produced from?
mitochondrial activity
TF is high levels of ROS always good for tumours?
no, initially increase proliferation. but if it goes over a toxic threshold the anti-oxidant capacity is overwhelmed and it leads to apoptosis
how can we use ROS as a anticancer therapy? 2 ways
stop inhibiting degluttathione metabolism
OR
increase amount of hydrogen peroxide
these will overwhelm the antioxidant capacity and lead to apoptosis
why can inhibiting FA synthesis be used as an anti cancer therapy?
FA is needed for proliferating cells
what does 2DG target?
hexokinases, hexokinases cant process 2GD so glycolysis cant continue
how can statins be used as anticancer therapy
targets mevalonate pathway
why is combination therapy Better? example of combination therapy here?
metformin +2DG
metformin+statins
combination is goo as tumours always adapt, combination covers more areas
