MIT’s John Essigmann calls his approach to fighting disease “fatal engineering.”

The name’s ironic but it also reflects a basic fact about cancer and other diseases: the best way to cure them is to engineer technologies that will kill diseased cells while sparing healthy ones.

Essigmann has spent years studying the cancer drug cisplatin. An agent made of platinum, chlorine and ammonia, cisplatin is one of medicine’s triumphs. It’s widely used to treat testicular cancer, which strikes about 6,000 U.S. men annually (and once afflicted the cyclist Lance Armstrong.) It’s also the main reason this cancer is rarely fatal.

“Cisplatin cures 19 out of 20 men with testicular cancer,” says the professor of chemistry and biological engineering. “Though almost never used by itself, it would still be strikingly effective if it were.”

Medical science hasn’t had much luck replicating that success. But Essigmann, who along with chemistry department chair Stephen Lippard is a cisplatin expert, hopes to change that by creating drugs based on a detailed grasp of how cisplatin attacks cancer.

Largely through the two MIT scientists’ efforts, the cisplatin story is being unraveled. In cancer cells, they’ve found, the drug is transformed into a derivative that clings tightly to DNA. Importantly, once bound to DNA it also links up with selected proteins already in the cell.

The binding of the so-called cisplatin-DNA adduct to a protein is critical. The protein-drug combination acts like an undercover police duo, with the protein standing guard while the platinum half of the pairing attacks the cell’s genetic machinery. “DNA repair-mechanisms can usually eliminate these adducts,” notes Essigmann, “but the protein shields them from repair.”

Essigmann knew that many proteins are over-expressed in cancer cells. Recognizing this fact, he wondered if he could design new drugs that would exploit this abundance. He took the problem to Robert Croy, his grad school lab mate and now a senior research scientist at MIT. “Bob asked, looking at the universe of cancers, which are known to have an overabundance of specific proteins?” says Essigmann. “Three types –– breast, ovarian and prostate –– immediately came to mind.”

As their first protein target, the pair chose the receptor, or in-cell anchor, for the hormone estrogen, long known to boost the growth of some ovarian and breast tumors. “Roughly half of breast cancers have an overabundance of the estrogen receptor,” notes Essigmann.

The researchers have created a molecule that’s like cisplatin in that it includes a cancer-fighting drug and connects to both the estrogen receptor and to DNA. Happily, the compound also combats cancer.

“It’s very effective at killing tumor cells in culture,” says Croy, who adds that preliminary evidence shows it fights tumors in lab rodents, too. And because it seems to provoke only modest side effects in animals, says Croy, “we’re now moving toward human clinical trials.”

Many infectious diseases feature proteins not normally found in our systems, so “fatal engineering” could aid in treating them as well as cancer. But Essigmann cautions that the extent of its effectiveness remains to be seen.

“We’re unlikely to develop a “magic bullet” that can cure cancer or any other disease on its own,” he adds. “But we’re creating something that could make a difference to many patients.”