Summary
Cellular senescence is a stable cell cycle arrest in response to various stressors, including DNA damage, oxidative stress and oncogene activation. Characterized by increasing levels of cyclin-dependent kinase inhibitors like p21Cip1/waf (CDKN1A) or p16Ink4a (CDKN2A), and a highly secretory state (senescence-associated secretory phenotype, SASP), these cells disrupt tissue homeostasis and promote inflammation as it is frequently found within the tumor microenvironment. Once thought as being implicated in cancer as a protective mechanism, particularly the SASP is now thought to promote tumor progression. This dual nature and the heterogeneity of the SASP itself open a wide field of questions regarding differences in cellular senescence per se and its multi-faceted role in the formation, progression and expansion of tumor cells. Deciphering common mechanisms within different tumor entities by which senescent cells effect their environment are the primary goal of the group.
Major Research Goals
- Elucidate the mechanisms by which senescent cells interact with other cells within the tumor microenvironment.
- Investigate how the SASP, and its heterogeneous composition, induces tumor growth and can be target pharmacologically.
- Identify the impact of senescent cells and their SASP on the tumor microenvironment and the formation of metastases, primarily within the bone.
- Determine therapeutic implications of senolytics in cancer.
Highlights
- Senescent cells secrete a cocktail of factors harming their environment that can be used to identify senescent cells in next-generation sequencing (NGS) datasets and monitor senolytic therapy (Nature article).
- The SASP in its heterogeneity is not just tissue-specific, but more likely depending on different senescent “subtypes” (bioRxiv preprint)
Outlook
Highlight the role of the senescence-associated secretory phenotype (SASP) in the formation of bone metastases.
Enlighten common mechanisms across different tumor entities in which senescent cells impact the tumor microenvironment via their SASP.
Identify molecular pathways within senescent cells that are analogous to those involved in tumorigenesis and can be targeted with senolytics like dasatinib + quercetin (D+Q).