Rigorous results of limiting behaviors of total tumor size under cyclic
intermittent therapy for the system of reversible phenotype-switchable tumor
cells
We are keenly interested in finding the limiting behaviors of total tumor
size when tumor cells are subject to the periodic repetition of therapy and
rest periods, called intermittent cyclic therapy. We hypothesize that each
tumor cell can take either therapy-sensitive or therapy-tolerant phenotype, its
phenotype transition is mainly driven by the presence or absence of
environmental stress, and such a transition is reversible. Even though those
aforementioned hypotheses make the model system simple, most of prior papers
attempted to numerically find the optimal therapeutic scheduling that minimizes
total tumor size, and there is no rigorous proof of the limiting behaviors of
total tumor size to my knowledge. Here we present such long-waited
mathematically rigorous results. In the first part of the paper, we present the
derivation of total tumor size reduction criterion and prove two theorems of
two different limiting behaviors of total tumor size under two different
therapy strategies, one leading to an asymptotic finite tumor size according to
an iterated map method and anther leading to asymptotically diminishing of
total tumor size. In the second part of the paper, we discuss the effects of
the intratumoral competition between sensitive and tolerant phenotypes on the
total tumor size reduction criterion