Irish researchers have discovered how cancers evade chemotherapy by entering a “zombie-like state”, offering hope for improved treatment options.
Scientists at Trinity College Dublin examined how cancerous tumours can escape the cell-killing effects of commonly used chemotherapy drugs by entering what is called premature senescence, which attracts the wound-healing properties of the immune system.
A person’s immune system plays a critical role in co-ordinating repair and replacement of damaged tissue, which is a process called wound healing.
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However, the researchers said cancers can exploit these wound healing capabilities for their own ends.
The cancers can masquerade as damaged tissue and trick the immune system into helping malignant cells to divide and acquire extra oxygen and nutrients rather than killing them.
They are often referred to as “zombie-like cells” because they have stopped dividing after treatment but do not die and continue to linger in the body and negatively affect the health of surrounding tissues.
For this reason, cancers have been described as “wounds that do not heal”.
However, how cancers switch on the wound healing capabilities of the immune system is still poorly understood.
The Trinity team found that molecules called Inhibitor of Apoptosis Proteins (IAPs) functioned in this setting by neutralising the cell-killing effects of molecules called “death receptors” that were switched on in response to DNA damage caused by chemotherapy.
Improved treatment options that neutralise more of these tumours promise to improve quality of life and survival rates, but to deliver these treatments, scientists need to understand how tumours function and where their weaknesses may lie.
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The research isolated a new mechanism that explains how some tumours evade death and use the body’s immune system to aid their recovery, as well as pinpointing promising new drug treatments, such as IAP antagonists, that kill them.
The research was led by Prof Seamus Martin, Smurfit professor of medical genetics, and Dr Gokhan Gunay, postdoctoral research fellow. Supported by the European Research Council and Research Ireland, it was published in the leading journal Science Advances.
“Discovering how tumours can evade the cell-killing effects of chemotherapy and enter senescence is an important and challenging problem,” said Martin.
“These new findings suggest ways in which we may be able to lower the defences of tumours by neutralising IAPs after the delivery of chemotherapeutic drugs, which should block their entry to senescence and kill more cells of the tumour.”