Abstract SY22-01: States of cell-cycle withdrawal

Abstract A key determinant of tumor recurrence is whether residual cancer cells that remain after treatment are in a reversible state of cell-cycle withdrawal (quiescence/dormancy) or an irreversible state of withdrawal (senescence). This distinction has been difficult to make because quiescent and senescent cells are defined by overlapping biomarkers and because cell-cycle withdrawal is much more poorly characterized than the cell cycle itself. While the reigning model in the field is that senescence and quiescence are entirely distinct states, our data suggest that senescence markers are expressed in a graded fashion, with signals that increase gradually as a function of time spent withdrawn from the cell cycle. We therefore favor an alternative model in which quiescence and senescence exist on a continuum of cell-cycle withdrawal where the probability of cell-cycle re-entry approaches zero at senescence. If we can quantify a cell’s depth-of-withdrawal, we could potentially predict the likelihood of cell-cycle re-entry and tumor recurrence, or push residual cancer cells into a deeper state of withdrawal. Citation Format: Sabrina L. Spencer. States of cell-cycle withdrawal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr SY22-01.