Abrupt transitions to tumor extinction: a phenotypic quasispecies model (Q2358406)

A defining feature of advanced tumors is their heterogeneity, stemming from the genetic instability associated with cancer cell proliferation, which is expressed through an increasing tendency of genome alteration during the lifecycle of the cancer cells. The competition between healthy cells (with a much lower mutation rate) and a heterogeneous population of cancer cell phenotypes consequently became an important topic in cancer research. Equally important is the competition between cancer cells of different phenotypes, as cancer cell populations reaching critical instability levels usually has lethal consequences. To address these issues, the authors propose and analyze a \(n\)-dimensional ODE model involving phenotypic quasispecies competition. Of concern are the stability of the equilibria and the catastrophic shifts (bifurcations), which involve abrupt transitions between tumor persistence and tumor clearance. The stability of the equilibria is analyzed via the linearized system, the bifurcation values being then derived and the corresponding bifurcation phenomena being characterized via extensive numerical simulations. It is proved that the increase of genomic instability favors the proliferation of cancer cells. A novel bifurcation, called \textit{trans-heteroclinic bifurcation}, which involves the exchange of stability between two equilibria which are placed away from each other and have a heteroclinic connection, is also observed to occur.