Inducing Senescence in Cancer: New Approaches for Harnessing a Stallion

Dr. Eichner’s lab studies LKB1 mutant lung cancer, a very deadly type of cancer which she feels may provide an important context for understanding the role that senescence, or the point at which cells are no longer able to divide and grow, might play in controlling cancer. Senescence is driven by three pathways: p53, RB and p65 (also called NF-kB). P53 and RB are understood to stop the cell cycle of replication and p65 drives the expression of a phenotype called the Senescence-Associated Secretory Phenotype (SASP) which recruits immune cells into the tissue microenvironment, causing targeted senescent cell self-clearance. Most studies of senescence in cancer have focused on p53 mutant cellular contexts, but Dr. Eichner suggests that study of senescence in cellular contexts that retain functional p53 is poised to uncover impactful discoveries.

The lung cancer driver Dr. Eichner studies is implicated in roughly 20% of lung adenocarcinoma (LUAD) and her lab recently found a histone deacetylase in LUAD that acts as a direct repressor of the SASP gene expression program. Building on this finding Dr. Eichner has developed a genetically engineered mouse model of LUAD that she feels will be an excellent way to further study senescence as a potential way to fight cancer. Her preliminary data shows that senescence in cells can be induced in LUAD tumors by targeting internal molecular regulators. Further, she suspects that she will be able to identify molecular mechanisms that regulate cell senescence. With her CRF Young Investigator Award, Dr. Eichner will employ a combination of RNA sequencing and CRISPR gene editing to determine which transcriptional mechanisms are regulating senescence and how metabolism contributes to the process. By identifying key regulators, she hopes to turn cell senescence into a therapeutic tool in lung cancer.