Novel Drug Stops Cancer Growth

A first-of-its-kind drug effectively targets a molecule that fuels cancer cells and shows promise for stopping the growth of tumors in their tracks.

The drug, Sphingomab, may even completely wipe out some tumors -- all while leaving healthy tissue alone, early laboratory and animal studies show.

If the findings can be repeated in humans, the experimental cancer drug may offer a new, highly targeted approach to fighting tumors with few side effects, says Gordon Mills, MD, PhD, chairman of molecular therapeutics at the University of Texas M.D. Anderson Cancer Center in Houston.

Multi-pronged Attack

Sphingomab zeroes in on a molecule that stimulates cancer growth known as sphingosine-1-phosphate, or S1P.

High levels of S1P have been found in tumor cells and have been associated with aggressive cancers that build up resistance to traditional chemotherapy drugs, says Roger Sabbadini, PhD, chief scientific officer of Lpath Therapeutics Inc., the San Diego-based company that makes the drug.

Reporting at the annual meeting of the American Association for Cancer Research, Sabbadini says that in excess, S1P is one of the really bad guys, instigating cancer spread in two distinct ways.

Cancer Sponge

"First, S1P has a direct effect on cancer cells, stimulating the cells to [grow and spread]," he tells WebMD. "But S1P also signals the growth of new blood vessels that feed a tumor."

Sphingomab works like a molecular sponge to soak up S1P so it can't do its dirty work.
In doing so, the drug fights cancer on multiple fronts, says Mills, who is helping to test Sphingomab.

"It puts the molecular brakes on the growth of [tumor-feeding] blood vessels, but it also blocks cell proliferation, cell survival, cell invasion, and the production of other factors that promote the growth of tumor cells and blood vessels."

Sphingomab is a monoclonal antibody. Antibodies are the body's natural defense against foreign substances, such as infection or cancer cells. Monoclonal antibodies are synthetic copycats that target a very specific portion of foreign substances. With such high precision, treatment is ideally more effective, with fewer side effects.

First Cancer Drug to Attack Lipid Molecule

What's really exciting, Mills tells WebMD, is that Sphingomab is the first drug to home in on one of the fatty molecules called lipids involved in cancer cell growth.

"We've known for a while that both lipid messengers and protein messengers are involved in cell growth. But all the existing drugs target proteins; no one has been able to figure out a way to target the lipids," Mills says.

That's really important, Sabbadini says, because cancer cells, particularly those that are resistant to standard chemotherapy, can mutate and make another version of the protein that the drug can't attack.

"You can't do that with lipids," he says. "There is only one form. If it mutates, it dies."

In mouse studies, Sphingomab completely eliminated about three-fifths of ovarian tumors and halted the growth of about half of lung and breast tumors and melanomas, Mill says. There were no side effects in the short-term studies, although the researchers caution that longer studies are needed.

Researchers Optimistic

Laboratory studies confirmed that Sphingomab has multiple modes of action: It both directly killed cancer cells and starved tumors to death by blocking the formation of blood vessels that feed them, Sabbadini says.

Researchers familiar with the ongoing studies are optimistic.

Sara A. Courtneidge, PhD, distinguished scientific researcher at the Van Andel Research Institute in Grand Rapids, Mich., and a keynote speaker at the cancer meeting, says targeting a lipid is an innovative approach to fighting cancer.

"That's what's really new here," she tells WebMD. "It's becoming increasingly clear that lipids also play an important role in cancer cell growth. Therefore targeting lipid molecules might represent a novel strategy in developing cancer treatments."

Sabbadini says the company hopes to start testing in humans by early 2007.

By Charlene Laino
Reviewed By Michael W. Smith, MD
© 2005, WebMD Inc. All rights reserved