Lab studies and several small clinical trials have suggested using chemotherapy to deliberately create new mutations in tumors may help fight cancer—but some researchers are wary.
Researchers are devising ways to paint targets on cancer cells. Drugs that unleash the immune system against cancer can be powerfully effective, but they appear to work best on the subset of tumors that are most riddled with mutations. Enter a controversial solution: Use chemotherapy to deliberately create new mutations in tumors and thereby make them more vulnerable to an immune system attack.
Drugs called checkpoint inhibitors remove a molecular brake that keeps immune sentries called T cells from attacking tumors. They work best on cancers such as lung tumors triggered by smoking-induced DNA damage and melanomas, which accumulate mutations from ultraviolet light. Many of these genetic changes cause cells to make “neoantigens,” novel protein fragments on tumor cells that flag them to T cells.
Postdoc Benoit Rousseau and others in the Diaz lab tested temozolomide and another chemotherapy drug, cisplatin, on cancer cells and found the combination produced 1000 times more frameshift mutations than either drug alone. When cancer cells treated with the drug combination were injected into mice, the resulting tumors vanished in response to a checkpoint drug.
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