Cytotoxic chemotherapy has long been a cornerstone in the treatment of advanced cancer. However, its efficacy is often hampered by the recurrence of tumors, both at the primary site and as metastases in other organs. Traditionally, this phenomenon has been attributed to the selection of drug-resistant cancer cells that survive the post chemotherapy treatment. Recently extensive research is investigating the more complex and paradoxical relationship between chemotherapy and cancer metastasis. Chemotherapy-induced metastasis refers to the phenomenon where chemotherapy, which is intended to treat cancer, may inadvertently contribute to the spread of the disease to new areas of the body. This can happen through a variety of mechanisms, such as the selection of resistant cells, changes to the tumor microenvironment, suppression of the immune system, and stimulation of processes like the epithelial-to-mesenchymal transition.
A recent study published in the journal Advanced Science by Dr. Xinjian Liu and colleagues has uncovered a fascinating and previously unrecognized aspect of chemotherapy-induced cancer recurrence and metastasis. They investigated the mechanisms behind chemotherapy-induced metastasis and highlights the crucial role of a unique subpopulation of cancer cells referred to as “near-death cells” (NDCs).
Traditionally, the process of chemotherapy-induced cell death has been considered irreversible once the plasma membrane integrity is compromised. However, Dr. Liu’s research challenges this notion. Their study reveals that a small subpopulation of cancer cells exposed to lethal doses of cytotoxins can survive and repopulate despite having compromised plasma membranes. These NDCs not only defy the conventional wisdom but also maintain chemosensitivity as parental cancer cells. What makes NDCs even more intriguing is that they acquire enhanced tumorigenic and metastatic capabilities compared to those of parental cancer cells. This paradoxical phenomenon raises important questions about the mechanisms driving the survival and proliferation of NDCs after exposure to cytotoxic chemotherapy.
Zhu C, Liu P, Li CY, Zhang Y, Yin J, Hou L, Zheng G, Liu X. Near-Death Cells Cause Chemotherapy-Induced Metastasis via ATF4-Mediated NF-κB Signaling Activation. Adv Sci (Weinh). 2023;10(10):e2205835. doi: 10.1002/advs.202205835.