Deciphering the Mechanisms of Therapy-Induced Senescence and Escape in Cancer

Therapy-induced senescence (TIS) in cancer is an emerging field of research that focuses on the cellular response of cancer cells to cytotoxic therapies. These therapies, which are designed to induce cell death, can instead lead to a state of senescence, characterized by cell cycle arrest and an inflammatory secretome. This phenomenon is similar to the senescence observed in benign fibroblasts and epithelial cells. However, TIS is increasingly recognized as a temporary state, with the potential for cells to escape and contribute to treatment resistance and disease recurrence. Recent studies have begun to unravel the complexities of TIS, highlighting the need for a deeper understanding of the mechanisms that govern the fate of these senescent cells. Despite the promising development of senolytic and senostatic strategies aimed at targeting TIS, there remains a significant gap in defining the TIS state across various cancer types and understanding the role of the TIS secretome in maintaining cell cycle arrest. Addressing these gaps is crucial for leveraging TIS to reduce cancer relapse.

This Research Topic aims to elucidate the mechanisms underlying therapy-induced senescence and the subsequent escape of cancer cells. The primary objectives include defining the TIS state in different cancer cell types, understanding the impact of the TIS secretome, and exploring the interactions between senescent cancer cells and their microenvironment. By addressing these questions, the research seeks to enhance the effectiveness of senolytic and senostatic therapies and minimize the risk of cancer recurrence.

To gather further insights into the mechanisms of therapy-induced senescence and escape in cancer, we welcome articles addressing, but not limited to, the following themes:
- Cellular components of TIS, including cell cycle plasticity, epigenetic reprogramming, and metabolic rewiring
- Heterogeneity of senescent cancer cells
- Interactions of senescent cancer cells with their microenvironment, such as stroma, microbiota, and hypoxia
- Innovative approaches for identifying senescent cancer cells
- Development of functional assays for senescence escape

Keywords: cancer, senescence, cell cycle, dormancy, secretome, senolytic, senostatic

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.