Dr. Einhorn takes on the Goliath of all cancers

By Karen Spataro

Thursday, September 12, 2013

In 1974, a young, unknown oncologist at the Indiana University School of Medicine added an experimental drug to the chemotherapy regimen for testicular cancer. Seemingly overnight, he turned the research world upside down, and a disease that was almost universally fatal became eminently curable.

More than three decades later, that same physician, Lawrence Einhorn, M.D., is older and grayer, but he retains the same enthusiasm for discovery he harbored as a young doctor. Only now he is focusing on the Goliath of all cancers.

“Lung cancer is the number-one cause of cancer death in America,” Einhorn says matter-of-factly while explaining his current fixation.

He is sitting behind a desk in his unassuming office in the Indiana University Melvin and Bren Simon Cancer Center. The smiling faces of patients whose lives have been touched by his ingenuity keep watch over him from photos that line the walls. Throughout his remarkable career, he has cured untold young men who otherwise would have succumbed to testis cancer, and he has given lung cancer patients precious more time. But he is determined to do better for the latter group.

“No one deserves to die from lung cancer,” says Einhorn, Indiana University Distinguished Professor.

He certainly has his work cut out for him. The odds of surviving a lung cancer diagnosis are slim. Once the cancer has spread, fewer than 4 percent of patients live to see another five birthdays. The result: Nearly 160,000 Americans are lost to the disease each year. That’s more than are killed by prostate, breast and colorectal cancers combined. Especially troubling is the fact that the disease is on the rise among nonsmokers, particularly young women.

Put simply, there are few good treatment options.

Perhaps not surprisingly, Einhorn suspects the answer to the vicious disease might involve platinum-based drugs — the same kind he used to revolutionize the treatment of testicular cancer. To that end, he has helped assemble a multidisciplinary team of researchers to figure out how to unlock the magic of platinum for lung cancer.

Unleashing the potential of platinum

CisplatinAs the name implies, drugs in this class are derived from the heavy metal platinum. Cisplatin — the first of these compounds — was developed in the 19th century, but wasn’t approved as a standard treatment for cancer until the 1970s, when Einhorn confirmed its incredible potential. Today, Cisplatin and subsequent generations of platinum drugs are used either alone or in combination to treat a host of cancers.

While platinum-based therapy has worked wonders for testis cancer, its success against many other malignancies has been less spectacular. In the case of lung cancer, the treatment is typically effective in the beginning. But inevitably, the cancer outsmarts the drug. When it does, the cancer comes back with a vengeance.

Einhorn and his team of IU researchers are trying to prevent that recurrence. To do so, they’ll first need to understand what’s happening in the tumor that allows it to evade the drug. This is where it gets tricky. Lung cancer can vary dramatically from person to person, and different tumors can have different survival techniques.

“The way that we’ll make real progress is by personalizing therapy,” Einhorn says.

With this in mind, the IU research group is focusing on platinum and exploring several ways to make the drug more effective.

Dr. John Turchi
Dr. John Turchi

Leading the charge in the laboratory is John Turchi, Ph.D., a biochemist who has studied platinum-based drugs for 15 years. Turchi was working at Wright State University School of Medicine in Ohio when his phone rang one day in 2004. He had given an exam to undergraduates and was fielding a barrage of complaints about grades. He suspected this call was yet another unhappy student. “I picked up the phone and said, ‘What do you want?’”

Einhorn was on the other end. What he wanted was for Turchi to come work with him at the IU Simon Cancer Center, and he had $1 million in philanthropic support lined up to build a world-class lung cancer research program. Turchi was shocked and humbled.

“It’s like being a banker and getting a call from Alan Greenspan,” Turchi says. He couldn’t say no.

Making headway in the lab

In the short time since, he and his IU colleagues have made remarkable progress.

Turchi’s laboratory studies the ability of tumor cells to repair themselves after Cisplatin treatment. By turning off that repair mechanism, Turchi hopes, the tumors will die. He has discovered three molecules — potential drugs — that show promise in the laboratory. Two have received provisional patents, and he’s working to move them along to patient trials.

His colleague, Jian-Ting Zhang, Ph.D., a pharmacologist, is investigating what triggers lung cancer aggression in the first place.