A Reporter Platform to Study Therapy-Induced Senescence in Live Cancer Cells.

Abstract

Senescence is a durable state of cell cycle arrest that can be induced by various stressors, including DNA damage caused by chemotherapeutic agents or ionizing radiation. In the context of cancer, therapy-induced senescence (TIS) plays a dual role: while it effectively halts tumor cell proliferation, TIS also carries the risk of promoting tumor relapse through the senescence-associated secretory phenotype (SASP). Beyond its direct impact on tumor cells, cancer therapies leading to TIS often induce short- and long-term side effects that significantly affect the quality of life for patients. However, the lack of universal biomarkers for TIS hinders a comprehensive understanding of its characteristics and its role in cancer therapies. A lamin-based senescence reporter platform is developed to reliably detect and sort live senescent cancer cells. This versatile tool supports live-cell imaging, enabling real-time tracking of senescence induction and escape to investigate heterogeneity in treatment response. Additionally, it allows high-content screening and marker integration, for example incorporating IL6 as SASP marker. It is therefore a valuable tool for fundamental research addressing new questions in the field of TIS as well as for drug discovery, including the development of novel senolytics.