  This paper introduces Cancer Hybrid Automata (CHAs), a formalism to model the
progression of cancers through discrete phenotypes. The classification of
cancer progression using discrete states like stages and hallmarks has become
common in the biology literature, but primarily as an organizing principle, and
not as an executable formalism. The precise computational model developed here
aims to exploit this untapped potential, namely, through automatic verification
of progression models (e.g., consistency, causal connections, etc.),
classification of unreachable or unstable states and computer-generated
(individualized or universal) therapy plans. The paper builds on a
phenomenological approach, and as such does not need to assume a model for the
biochemistry of the underlying natural progression. Rather, it abstractly
models transition timings between states as well as the effects of drugs and
clinical tests, and thus allows formalization of temporal statements about the
progression as well as notions of timed therapies. The model proposed here is
ultimately based on hybrid automata, and we show how existing controller
synthesis algorithms can be generalized to CHA models, so that therapies can be
generated automatically. Throughout this paper we use cancer hallmarks to
represent the discrete states through which cancer progresses, but other
notions of discretely or continuously varying state formalisms could also be
used to derive similar therapies.
