PT  - JOURNAL ARTICLE
AU  - Ryan J. Murphy
AU  - Gency Gunasingh
AU  - Nikolas K. Haass
AU  - Matthew J. Simpson
TI  - Growth and adaptation mechanisms of tumour spheroids with time-dependent oxygen availability
AID  - 10.1101/2022.04.24.489294
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.04.24.489294
4099  - http://biorxiv.org/content/early/2022/04/24/2022.04.24.489294.short
4100  - http://biorxiv.org/content/early/2022/04/24/2022.04.24.489294.full
AB  - Tumours are subject to external environmental variability. However, in vitro tumour spheroid experiments, used to understand cancer progression and develop cancer therapies, have been routinely performed for the past fifty years in constant external environments. Furthermore, spheroids are typically grown in ambient atmospheric oxygen (normoxia), whereas most in vivo tumours exist in hypoxic environments. Therefore, there are clear discrepancies between in vitro and in vivo conditions. We explore these discrepancies by combining tools from experimental biology, mathematical modelling, and statistical uncertainty quantification. Focusing on oxygen variability to develop our framework, we reveal key biological mechanisms governing tumour spheroid growth. Growing spheroids in time-dependent conditions, we identify and quantify novel biological adaptation mechanisms, including unexpected necrotic core removal, and transient reversal of the tumour spheroid growth phases.Competing Interest StatementThe authors have declared no competing interest.