Epigenetic modifications to "convert" tumor cells into healthy ones

[Ben99]

Hello,

Few days ago I had a doubt; can we use epigenetic modifications on a tumor cell in order to bring it back to a healthy condition? ( so acting only on the epigenome and not varying the genome).

On the other hand can we also use epigenetic modification on a healthy cell to transform it into a tumor one? ( is like the reverse of the first question above this one ) 

how can we perform both of the possible scenarios shown above (if it is possible to do these transformations ) 

Edited April 24, 2020 by Ben99

[Dagl1]

Probably not, epigenetic modifications can induce transcriptional changes, but if a tumor has a mutation in a gene necessary for its survival, then epigenetic modifications will not help to get around that mutation. Of course, you could alter some characteristics of the tumor (but it will probably be changing those back), but you cannot bring it back to an healthy condition without changing the genome as far as I can think of. 

How one would do that is even more difficult, you would have to induce methylation and histone modifications at many many sites, additonally you might want to change the location of the DNA within the nucleus to be closer or further away from the nuclear lamina. Some of these things you could do with very targeted dCas9 systems, which recruit factors. But then you would have to provide possibly hundred if not thousands of sgRNAs, and the question is if that would work. At that point it might be easier to 'just' try to find and edit away every mutation.

Maybe other people can think of some ways that you can do this, but I myself can't come up with any way. 

[Ben99]

1 minute ago, Dagl1 said:

Probably not, epigenetic modifications can induce transcriptional changes, but if a tumor has a mutation in a gene necessary for its survival, then epigenetic modifications will not help to get around that mutation. Of course, you could alter some characteristics of the tumor (but it will probably be changing those back), but you cannot bring it back to an healthy condition without changing the genome as far as I can think of. 

How one would do that is even more difficult, you would have to induce methylation and histone modifications at many many sites, additonally you might want to change the location of the DNA within the nucleus to be closer or further away from the nuclear lamina. Some of these things you could do with very targeted dCas9 systems, which recruit factors. But then you would have to provide possibly hundred if not thousands of sgRNAs, and the question is if that would work. At that point it might be easier to 'just' try to find and edit away every mutation.

Maybe other people can think of some ways that you can do this, but I myself can't come up with any way. 

I just edited my question because it was not complete, my bad:(

Anyway thank you for your answer. 

[Dagl1]

I think converting a healthy cell into one growing out of control, could be possible through epigenetic means. Highly increase transcriptional activity of growth-related genes, possibly decrease surveillance genes. Whether that would work (and not induce apoptosis or other forms of cell death), I am not sure about. But please note that tumors are generally mutating a lot. So even if you could start inducing a cell to become a tumor cell, being a tumor cells means mutating a lot. So at that point we are not really only within the epigenetic realm.

Either way, I don't think we currently can do this, but I feel that in theory, creating uncontrolled growth through epigentic means is more feasible than turning tumor cells into non-tumor cells (but I suppose that uncontrolled growth is not exactly the same as being a tumor, so not sure if that really counts in your eyes).