Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>Human aging is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Whether aging as its own entity can be initiator of putative cancerous developments, the transcriptional changes underlying the cancerous development itself are largely unknown. Here, we analyzed publicly available bulk RNA sequencing data of 328 control vs. 453 cancer samples in combination with single cell sequencing datasets from 49 control vs. 105 cancer patients. Using widely accepted aging-associated gene sets, we assembled key features of aging and their reflection in cancer development in five distinct cancer entities with an age-dependent increase of incidence, i.e. chronic myeloid leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC) and pancreatic ductal adenocarcinoma (PDAC). After confirmation of the aging/senescence-induced gene (ASIG) expression to be upregulated in malignant diseases compared to healthy controls, we elucidated the importance of ASIGs during single cell development, making use of pseudotime analyses. In each entity, distinct temporally late enrichment states were carved out, and their transcriptional connectivity next to epigenetic control verified. Remarkably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. Except for pancreatic cancer, all entities accounted for subpopulations with aging associated patterns. Using a novel pipeline to repurpose FDA-approved drugs and combinations on a single cell level, we discovered a path for novel treatment regimen on a tumor-specific basis. These respective cellular subpopulations demonstrate pillars of susceptibility within the complex tumor microenvironment and serve as a basis for future studies on the role of aging and senescence in human malignancies.</jats:p>
<jats:p>Citation Format: Dominik Saul, Robyn Laura Kosinsky. Aging patterns in five disparate cancer entities indicate a novel senescent cell population with therapeutic targetability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5024.</jats:p>