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Could you simultaneously target multiple mutations to reduce the risk of this? Similarly to using a cocktail of antibiotics to prevent the development of resistance.

i.e. the probability of shedding a single mutation is 1/x, but the probability of shedding two in the same organism is (1/x)^2, so targeting more mutations make it exponentially harder for the organism to adapt.

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Yes, this reasoning is correct. Same principle applies to combination therapies for HIV, malaria, etc., where you're at risk of developing a resistant strain within the patient. Not sure why it isn't more common among cancer therapies. Maybe not enough unique targets?

Not enough unique drugs, difficulty determining mutations/susceptibility of tumour to drug, high side effect profile of drugs used in isolation and higher still in combination

Can you turn off a mutation's ability to adapt and mutate?

It would be called killing the tumour. The only way to destroy mutation is to destroy replication. We don't know how to increase the fidelity of DNA replication, and cancer cells have their error correct mechanisms all destroyed

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