Importance of germline and somatic genomic mutations to the purpose of treatment in cancer

Question

Is there a hierarchy in the sets of genomic mutations (somatic and germline) to the purpose of treatment in cancer?

Can they be considered at the same level in the context of targeted therapy or are there reasons to prioritise one set vs the other?

Answer 1

A) There isn't really a fixed hierarchy that is applicable across the board - alterations are often binned into actionable targets and non-actionable ones. In terms of customised cancer vaccine for immunotherapy (Eg - www.sciencemag.org/news/2017/04/personalized-tumor-vaccines-keep-cancer-check ) , more antigenic mutations tend to be prioritised.

B) Sometimes there are reasons to prioritise mutations over others even for small molecule targeted therapies. For example, one would want to target mutations that are clonal rather than subclonal where possible, so that the bulk of the tumour, rather than a small fraction of the cells in it, are targeted. Alternatively where one has, for example, a resistance mutation arising from prior therapy (You see this with EGFR T970M mutations) it is an indication for next generation EGFR inhibitors that specifically hit the resistant mutation.