Hope For Late-Stage Lung Cancer? Two-Drug Combo Activates Genes That Help Tumors Self-Destruct

Researchers from Case Western Reserve University School of Medicine and Mount Sinai School of Medicine found that the anti-psychotic medication trifluoperazine can reactivate a gene pathway involved in tumor suppression that's normally turned off in lung cancer patients.

When combined with the targeted lung cancer drug erlotinib, it could be a potent treatment, the researchers said on Friday in the Journal of Clinical Investigation.

Through experiments in human cells, human lung cancer tissue and mouse lung tissue, the team found that trifluoperazine was able to stop the product of a gene called FOXO1 from being taken out of a tumor cell's nucleus. By keeping FOXO1 in the nucleus of the cell, it can activate KFL6, another gene that kicks of a molecular signaling cascade that ends with the destruction of the tumor cell.

Basically we're able to make FOXO1 turn on KLF6, which tells cancer cells to die, senior author Goutham Narla said in a telephone interview.

When the researchers gave mice that were injected with human lung cancer cells trifluoperazine in combination with the targeted lung cancer drug erlotnib, the tumors shrank much more than in mice treated with either drug by itself.

Both drugs are already approved by the US Food and Drug Administration - erlotinib is sold under the brand name Tarceva and trifluoperazine is marketed under the brand name Stelazine.

Narla says he and his colleagues are working to develop a clinical trial examining how the two-drug combination fares in human patients.

One of the advantages to this approach is it can be immediately translated into clinical trials, Narla says.

Normally, the path to producing a new drug is long and fraught with failures. But since both drugs have already passed safety tests on their way to their original FDA approval, trials in humans could start by the end of 2012, according to Narla.

The anti-psychotic drug could also be potentially used to combat other kinds of tumors, since the FOXO1 and KLF6 defects found in lung cancer are also seen in some breast and prostate cancers.

We can imagine using this combination -- not with Tarceva, since that's specific to lung cancer -- in other cancers to activate this particular network, Narla said.