Allee Effect and Oncolytic Virotherapy: Different Therapeutic Outcomes for Different Tumour Growth.

Tumour recurrence after oncolytic virotherapy is a critical clinical challenge, as solid cancers tend to persist and spread after such therapies alone. Often, mathematical models consider tumour growth without taking possible cooperative cell behaviours into account. Instead, the well-known Allee effect has the ability to drive low-density tumour dynamics and affect therapeutic outcomes. For this reason, we here explore the contribution of Allee effects into two of the most common cancer growth paradigms, e.g. the logistic and the Gompertz frameworks. Our analysis reveals that density-dependent cooperation fundamentally alters virotherapy efficacy. Weak effects can enable pseudo-extinction states where tumour populations collapse to undetectable levels, whilst strong effects can interestingly create non trivial, bistable outcomes. Initial tumour burden seems to be determinant: bifurcation analysis shows scenarios where modest increase in infection or decrease in clearance rates can shift outcomes dramatically. Notably, the Gompertz model exhibits multistability under marginal Allee thresholds, pointing at a possible explanation for spontaneous remission that have been clinically observed. Overall, these findings suggest that Allee effects may be an important factor in the future to adjust dosing schedules, reduce viral loads, lower recurrence risk and shorten therapeutic times. Our framework may also offer quantitative guidance for patient-specific regimes for virotherapy and combination therapies.