Stochastic fluctuations in apoptotic threshold of tumour cells can enhance apoptosis and combat fractional killing.

ABSTRACT: Fractional killing, which is a significant impediment to successful chemotherapy, is observed even in a population of genetically identical cancer cells exposed to apoptosis-inducing agents. This phenomenon arises not from genetic mutation but from cell-to-cell variation in the activation timing and level of the proteins that regulates apoptosis. To understand the mechanism behind the phenomenon, we formulate complex fractional killing processes as a first-passage time (FPT) problem with a stochastically fluctuating boundary. Analytical calculations are performed for the FPT distribution in a toy model of stochastic p53 gene expression, where the cancer cell is killed only when the p53 expression level crosses an active apoptotic threshold. Counterintuitively, we find that threshold fluctu

SUBMITTER: Qiu B 

PROVIDER: S-EPMC7062090 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature