Cellular senescence in normal cells is a potent stress response to telomere shortening, oncogene activation and DNA-damaging agents, and prevents the proliferation of damaged cells. Despite the initial discovery of cellular senescence by Leonard Hayflick six decades ago, a universal biomarker is still currently lacking and the use of a combination of multiple markers is typically required to reliably identify senescent cells.

Notably, several hallmarks of senescence have been characterised in normal fibroblast or epithelial cells including cell cycle arrest via activation of the p53 and RB signalling pathways, increased cell size and flattening, senescence-associated beta-galactosidase (SA-b-gal) activity, heterochromatic foci (SAHF) and a secretory phenotype (SASP). Cancer cells, despite having developed the means to bypass known cell cycle arrest checkpoints, can still undergo therapy-induced senescence, displaying classical senescence hallmarks in response to many conventional and targeted therapies. However, therapy-induced senescent cancer cells can be detrimental, harbouring adverse features that may cause therapy resistance and cancer recurrence, namely apoptosis resistance, the ability to re-enter the cell cycle, and the secretion of immunosuppressive factors. Hence, strategies to selectively eliminate therapy-induced senescent cancer cells using senolytic drugs or to reprogram the SASP are emerging.

To realise the clinical potential of strategies harnessing senescence to target cancer, it is imperative to understand the full spectrum of the senescence response in a range of cancer types and genetic backgrounds. Furthermore, this will require innovative methods to identify senescent cells and technologies to interrogate the mechanistic underpinnings of their phenotypes in both cell and preclinical animal models.

The aim of this Methods Collection is to invite protocols that include, but are not limited to, microscopy, flow cytometry, high-throughput screening, and omics-based approaches to facilitate the investigation of senescence in cancer.