MLL1, Aging, Cancer, And Inflammation

Here are the key points concerning an enzyme linking aging, inflammation, and cancer, with possible therapeutic implications:
 

Aged and damaged cells frequently undergo a form of proliferation arrest called cellular senescence. These fading cells increase in human tissues with aging and are thought to contribute to age-related increases in both cancer and inflammation. The secretion of such inflammatory compounds as cytokines, growth factors, and proteases is called the senescence-associated secretory phenotype, or SASP.

"Since tumor-promoting inflammation is one of the hallmarks of cancer, these findings suggest that MLL1 inhibitors may be highly potent anti-cancer drugs through both direct epigenetic effects on proliferation-promoting genes, as well as through the inhibition of inflammation in the tumor microenvironment," says first author Brian Capell, MD, PhD, a medical fellow in the lab of Shelley Berger, PhD, the Daniel S. Och University Professor in the Departments of Cell & Developmental Biology, Genetics , and Biology.

Knowing that MLL1 has been implicated in cell-cycle regulation, when the researchers inhibited MLL1, proliferation-promoting genes were shut down and the DNA damage response and resulting inflammation was suppressed. Indeed, in the case of applying this result to fighting cancer, this is a desired effect, since an increase in inflammation can promote both the development and progression of cancer.

"In cancer, this could be a potent one-two punch, by blocking both proliferation-promoting genes as well as the cancerous inflammation," Capell explained. "One could imagine taking an MLL1 inhibitor as a primary treatment, but also as an adjuvant therapy to tamp down the rampant inflammation caused by drugs like chemotherapies. More speculatively, given that the SASP has been implicated in numerous other age-related disorders, it will be worth testing the effects of MLL1 inhibition in other aging and inflammatory disease models."