A new drug target for lung cancer
Drugs targeting an enzyme involved in inflammation might offer a new way to treat certain lung cancers, according to a new study from the lab of Inder Verma. His team discovered that blocking the activity of an enzyme that helps activate the body's inflammation response slowed the growth of tumors in mice with lung cancer and increased their lifespan.
"Lung cancer is one of the most lethal cancers, and the prognosis for patients is often poor, with only about 15 percent surviving more than five years," Verma says.
Scientists have long known that there is a link between cancer and inflammation, the body's first line of defense against infection. Some of the same biochemical players that protect the body by controlling cells' inflammation response can also be hijacked by genetic mutations involved in the development of cancer. To better understand how these normally helpful components of the immune system are put to nefarious tasks in cancer cells, Verma and his colleagues developed a new method of inducing non-small-cell lung cancer in mice. This type accounts for as much as 80 percent of all lung cancer cases.
They then turned their attention to a protein complex, NF-KB, that initiates the inflammation response to infection by orchestrating a cell's genetic activity. Malfunctioning regulation of NF-KB has been linked to various types of cancer, including lung cancer, but due to its many functions in the cell, drugs that directly target NF-KB would likely cause severe side effects.
To get around this limitation, Verma's group focused on IKK2, an enzyme that spurs NF-KB's activity in response to stress. When they blocked IKK2 activity in the mice with lung cancer, the mice had smaller tumors and lived longer, suggesting that the enzyme is necessary for NF-KB to stimulate tumor growth. This was unexpected because the conventional wisdom is that loss of NF-NB activity will reduce inflammation.
The findings, reported in Nature Cell Biology, suggest that drugs that hinder IKK2's ability to command cellular activity might prove effective as lung cancer therapies.
"Systemically and chronically blocking IKK2 activity is too toxic to be used in chemotherapy," says Yifeng Xia, a postdoctoral researcher in Verma's lab, "but we might be able to target another molecule in the signaling pathway by which IKK2 regulates tumor growth."