  Cancer development is driven by mutations and selective forces, including the
action of the immune system and interspecific competition. When administered to
patients, anti-cancer therapies affect the development and dynamics of tumours,
possibly with various degrees of resistance due to immunoediting and
microenvironment. Tumours are able to express a variety of competing phenotypes
with different attributes and thus respond differently to various anti-cancer
therapies. In this paper, a mathematical framework incorporating a system of
delay differential equations for the immune system activation cycle and an
agent-based approach for tumour-immune interaction is presented. The focus is
on those metastatic, secondary solid lesions that are still undetected and
non-vascularised. By using available experimental data, we analyse the effects
of combination therapies on these lesions and investigate the role of mutations
on the rates of success of common treatments. Findings show that mutations,
growth properties and immunoediting influence therapies' outcomes in nonlinear
and complex ways, affecting cancer lesion morphologies, phenotypical
compositions and overall proliferation patterns. Cascade effects on final
outcomes for secondary lesions are also investigated, showing that actions on
primary lesions could sometimes result in unexpected clearances of secondary
tumours. This outcome is strongly dependent on the clonal composition of the
primary and secondary masses and is shown to allow, in some cases, the control
of the disease for years.
