Study Finds How Tumors Evade Chemotherapy

Researchers from the Smurfit Institute of Genetics at Trinity College Dublin identified how some tumor cells survive chemotherapy. Led by Prof. Seamus Martin and Dr. Gokhan Gunay, the team found that Inhibitor of Apoptosis Proteins neutralize Death Receptors switched on by chemotherapy-induced DNA damage. Surviving cells enter premature senescence, a non-dividing but metabolically active state. Within a few days they become almost 10 times bigger than a normal cell, ramp up wound-healing genes, and secrete inflammatory mediators that attract immune cells. The study was published in Science Advances (DOI 10.1126/sciadv.aed4541). Senescent cells proved highly dependent on IAPs for survival. IAP antagonist compounds selectively eliminated them by reactivating the Death Receptor self-destruct program. Prof. Seamus Martin said: "Discovering how tumors can evade the cell-killing effects of chemotherapy and enter senescence is an important and challenging problem." He said: "These new findings suggest ways in which we may be able to lower the defenses of tumors by neutralising IAPs after the delivery of chemotherapeutic drugs, which should block their entry to senescence and kill more cells of the tumor." The findings clarify a survival path and a lab vulnerability; they do not establish that an improved treatment is available now.