Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

A non-genetic, cell cycle-dependent mechanism of platinum resistance in lung adenocarcinoma


We previously used a pulse-based in vitro assay to unveil targetable signalling pathways associated with innate cisplatin resistance in lung adenocarcinoma (Hastings et al., 2020). Here, we advanced this model system and identified a non-genetic mechanism of resistance that drives recovery and regrowth in a subset of cells. Using RNAseq and a suite of biosensors to track single-cell fates both in vitro and in vivo, we identified that early S phase cells have a greater ability to maintain proliferative capacity, which correlated with reduced DNA damage over multiple generations. In contrast, cells in G1, late S or those treated with PARP/RAD51 inhibitors, maintained higher levels of DNA damage and underwent prolonged S/G2 phase arrest and senescence. Combined with our previous work, these data indicate that there is a non-genetic mechanism of resistance in human lung adenocarcinoma that is dependent on the cell cycle stage at the time of cisplatin exposure.

Type Journal
ISBN 2050-084X (Electronic) 2050-084X (Linking)
Authors Gonzalez Rajal, A.; Marzec, K. A.; McCloy, R. A.; Nobis, M.; Chin, V.; Hastings, J. F.; Lai, K.; Kennerson, M.; Hughes, W. E.; Vaghjiani, V.; Timpson, P.; Cain, J. E.; Watkins, D. N.; Croucher, D. R.; Burgess, A.
Responsible Garvan Author A/Prof David Croucher
Publisher Name eLife
Published Date 2021-05-31
Published Volume 10
Status Published in-print
DOI 10.7554/eLife.65234
URL link to publisher's version