The most recent research exploring how cell death and cellular senescence interact within the context of cancer, along with their pathophysiological implications, has been summarized.
As cells age, they release substances that can encourage the growth of cancer cells. Efforts are underway to develop drugs that either specifically target and destroy these aging cells or inhibit their substance secretion. A team from Osaka Metropolitan University’s Graduate School of Medicine, in collaboration with Harvard Medical School, has reviewed the latest findings about the interaction between cell death and cellular senescence in cancer and their significance in disease processes.
Dr. Kouhei Shimizu and Professor Fuminori Tokunaga from OMU, along with Dr. Hiroyuki Inuzuka from Harvard, highlighted the molecular processes involved in different forms of cell death and the modifications to their regulatory factors as cells get older.
Since senescent cells have a tendency to resist apoptosis, the most well-studied form of programmed cell death, overcoming this resistance has become a key focus in therapies aimed at eliminating senescent cells. However, the regulation of emerging inflammatory forms of programmed cell death like necroptosis, pyroptosis, and ferroptosis—whose molecular mechanisms have recently been clarified—within senescent cells is still not well understood.
There remain numerous questions regarding whether therapies, including those that target and remove senescent cells or senomorphics—which aim to address harmful aspects of the senescence-associated secretory phenotype without eliminating the cells—can be effectively applied to these newer forms of programmed cell death. Current understanding in these areas is limited.
Dr. Shimizu commented, “In the past ten years, research into cell death has significantly advanced, but its connection to cellular senescence remains unclear. Different types of cell death may offer valuable opportunities for preventing and treating cancer and age-related illnesses. We hope this review serves to foster understanding of effective cell death mechanisms against senescent cells and lead to the development of strategies that curb the release of detrimental substances.”
The findings have been published in Seminars in Cancer Biology.
