Research News

Latest findings on the significance and interaction between cell death and cellular senescence in cancer

How a drug might prevent cancer formation

A drug could induce programmed cell death in senescent cells expressing SASP factors.

Credit: Osaka Metropolitan University

Aging cells secrete substances known to promote the growth of cancer cells. The development of drugs that can selectively kill these cells or inhibit the secretion of substances is ongoing. The latest findings on the interaction between cell death and cellular senescence in cancer and their pathophysiological significance have been reviewed by a team from Osaka Metropolitan University’s Graduate School of Medicine and Harvard Medical School.

Lecturer Kouhei Shimizu and Professor Fuminori Tokunaga of OMU and Dr. Hiroyuki Inuzuka of Harvard Medical School outlined the molecular mechanisms of various types of cell death and the changes in their regulatory factors that occur with age.

Since senescent cells often have resistance to apoptosis, the best characterized programmed cell death, the removal of this resistance has been a major goal of senescent cell removal therapy. On the other hand, it is not yet known how the relatively new types of inflammatory programmed cell death, such as necroptosis, pyroptosis, and ferroptosis, the molecular mechanisms of which have been rapidly elucidated in recent years, are regulated in senescent cells.

There are also many questions about whether therapies such as senescent cell removal therapy and senomorphics—drugs that only target the harmful senescence-associated secretory phenotype without killing the senescent cells—can be applied to these new types of programmed cell death, and there is little understanding of these either.

“In the last decade, the emerging field of cell death research has developed dramatically, but the relationship with cellular senescence is still undefined,” Dr. Shimizu stated. “Various types of cell death are thought to have great potential as targets for the prevention and treatment of cancer and age-related diseases. We hope this review will accelerate the elucidation of cell death that is effective against senescent cells and the development of methods to inhibit the secretion of harmful substances.”

The findings were published in Seminars in Cancer Biology.

Funding

This work was partly supported by funding from ACT-X, JST (JPMJAX2117 to K.S.) and MEXT/JSPS KAKENHI (JP20K16146 and JP22K07174 to K.S., and JP24K02242 and JP22K18385 to F.T.).

Paper information

Journal: Seminars in Cancer Biology
Title: The interplay between cell death and senescence in cancer
DOI: 10.1016/j.semcancer.2024.11.001
Authors:  Kouhei Shimizu, Hiroyuki Inuzuka, Fuminori Tokunaga
Published: 16 November 2024
URL: https://doi.org/10.1016/j.semcancer.2024.11.001

Contact

Kouhei Shimizu

Graduate School of Medicine
shimizu.kouhei [at]omu.ac.jp

*Please change [at] to @.