Tumour repopulation and the role of abortive division in squamous cell carcinomas during chemotherapy

In head and neck cancers, tumour cell repopulation during chemotherapy is one reason for treatment failure. Some of the mechanisms responsible for this repopulation are cell recruitment and abortive division. Due to lack of quantitative data in the literature regarding these mechanisms, the aim of this study was to investigate the interplay between recruitment and abortive division during cisplatin chemotherapy and to quantify the impact of these mechanisms on tumour control.

An in silico Monte Carlo tumour model was developed to simulate tumour behaviour during chemotherapy. The virtual tumour had the composition and kinetic properties of a biological tumour. Effect of cisplatin on cell cycle and repopulation mechanisms were simulated and interpreted.

Abortive division contributed to cell production within the tumour during chemotherapy. There was a strong relationship between recruitment and tumour growth due to abortive division. This observation was supported by the value of proliferative/stem ratio, which increased from 1.3 to 36, even when using small recruitment parameters.

While abortive division contributed towards tumour repopulation during chemotherapy, this mechanism could be controlled by daily doses of cisplatin. On the other hand, stem cells require an additional cytotoxic agent to overcome repopulation due to cell recruitment. Consequently, repopulation via abortive division during chemotherapy did not entail alterations in treatment schedule, nor dose escalation, to control the tumour.