In a trailer for a YouTube series about dealing with cancer, one patient complains, “You’re putting crap into your body to get rid of crap that’s in your body, you know, and it’s very frustrating.”
Many share this cancer patient’s frustration with the poisonous side effects of chemotherapy. Yet, efforts to identify a “silver bullet” that would kill cancer cells while leaving everything else in the body alone have been consistently disappointing.
But one experimental drug shows early signs of achieving that goal, according to a paper published today in the journal Science Translational Medicine. The drug, called OTS964, completely eliminated aggressive human lung cancer tumors in five out of six mice without major side effects, University of Chicago researchers working with the Japanese pharmaceutical company OncoTherapy Science report.
“Many drugs can repress the growth, but it is uncommon to see them eradicated. This has rarely been reported,” senior author Dr. Yusuke Nakamura, deputy director of the Center for Personalized Therapeutics at the University of Chicago, said in a press statement.
Hitting a Small Target
OTS964 is a chemical compound that targets an enzyme, called T-lymphokine-activated killer cell, or TOPK, that cancer cells use to divide and spread. In several forms of cancer, including blood and triple-negative breast cancers, higher levels of the enzyme signal worse health outcomes. And because healthy cells rarely use the enzyme, side effects could be minimal.
For almost a decade after they identified TOPK as a target, the researchers have looked for a drug that would successfully knock it out. In 2012, another group reported that they’d found a drug targeting TOPK that shrunk tumors by 60 percent.
A few years ago, Nakamura and his colleagues began testing an earlier formulation of the current drug. They found that it worked, but it interfered with the production of blood cells. In the current study, the researchers encased the drug agent in bubbles called liposomes to reduce side effects.
When they saw that the conventional intravenous form worked well, the researchers tried an oral formulation that would, hypothetically, let patients take the drug from home. The oral formula led to a temporary drop in white blood cells but still shrunk tumors dramatically.
A Mouse or a Man?
The researchers must now see how human patients respond. There is one part of the body that uses the cell-division enzyme TOPK: the testes. The researchers are thus aware that fertility side effects might crop up, said co-author Jae-Hyun Park, a research associate in the department of medicine at the University of Chicago.
A phase 1 clinical trial is planned for the fall of 2015. The trial will try the drug against leukemia. In addition to lung cancer, some forms of leukemia, brain, liver, and bladder cancers also have high levels of the enzyme TOPK.
OTS964 could well end up on the cutting room floor of medical research. But it’s a first step toward the vision of an effective cancer drug that’s as simple for patients to take as an antibiotic.