Cancer Specialist Teams With VAI

GRAND RAPIDS — Research collaboration struck last year between the Van Andel Research Institute and a physician known worldwide for curing testicular cancer has produced its first scientific study.

Lawrence Einhorn, M.D., professor of medicine at Indiana University, has been collaborating with VARI Senior Scientific Investigator Bin Tean Teh, M.D., Ph.D., since early 2002, applying the institute’s expertise in kidney cancer research to the study of testicular cancer.

Einhorn began developing a chemotherapy regimen in 1974 that now effectively cures 90 percent of all testicular cancer, the most common form of cancer among men age 15 to 35. He’s perhaps best known for curing Lance Armstrong, the Olympic cyclist and four-time Tour de France champion.

“Testicular cancer is unique among all cancers that we treat with chemotherapy because the overwhelming majority of young men who have this disease are cured. That’s not true with any other cancer,” Einhorn said.

“Discoveries that are made that work for this very rare disease have universal application for other cancers as well.”

Since Einhorn and Teh teamed up, they’ve been trying to determine why the remaining 10 percent of testicular cancer patients are resistant to therapy.

What Einhorn has found is that there is a group of testicular cancer patients that behave like regular cancer patients: They go on chemotherapy, respond and get better, then the disease comes back and they die. That’s what happens with most cancers in 2003, Einhorn said.

So the focus is on that group of testicular patients that have “late relapse.” They receive therapy, do well for a couple years and then the cancer comes back. Though patients in the late relapse category respond to therapy, they’re not being cured.

“This is a very peculiar phenomenon that Dr. Einhorn observed,” Teh said. “We believe it must be due to some genetic profile. If we identify them, we obviously can use it for predicting some of these cases.”

When the cancer returns, it looks the same under the microscope but, biologically, there’s something very different about it, Einhorn observed.

So their goal is to find out what is the difference, biologically, between a patient who has a late relapse vs. a patient with ordinary, newly diagnosed testicular cancer.

Step No. 1 is to pinpoint the molecular difference, Einhorn said. It’s like working on a jigsaw puzzle; step one is the first piece and as each connecting piece is added, the big picture begins to take shape.

He and Teh have studied about 20 cases and their findings will soon be published in the peer-reviewed journals. Though 20 cases don’t constitute a large study, they do make for a good pilot study, Teh said.

All the patients in the study had been successfully treated for testicular cancer initially. One group relapsed and developed new tumors within two years, while the other group relapsed after more than two years.

The genetic profiles of the tumors may explain why they are resistant to chemotherapy, Teh said. So he’s involved with gene expression, trying to develop a molecular fingerprint to identify what is different about these patients compared to newly diagnosed patients.

“Once we find out what Bin finds out — what the difference is — then we hope we can exploit that difference therapeutically and develop novel therapy for this group of patients,” Einhorn said.

“It’s great studying testicular cancer with Dr. Einhorn because he has the largest number of patients and that’s why we approached them,” Teh noted, adding that Einhorn, in turn, was very impressed with VARI’s kidney cancer research.

“We are actually very well known for our kidney cancer work, and because we have that experience, we thought we could use this technology we have already shown in kidney cancer and apply it to testicular cancer. That’s why I approached Dr. Einhorn and his associates.”

In the area of urological oncology — kidney, testicular, prostate and bladder cancer — Teh and his group have done the pivotal studies in the world in looking at gene expression in kidney cancer patients, Einhorn said.

In his war on testicular cancer, Einhorn also has formed collaborations with Indiana University’s School of Medicine, where he has taught since 1973, and a collaboration with an investigator in New Mexico, as well as with an investigator at Dartmouth.

The VAI is his first private institution collaboration.

“Bin has been very generous with his time in coming down to Indiana University, working with my urology colleague, Dr. Richard Foster, and myself. It’s been an excellent collaboration. I think when you’re looking at a perfect collaboration, in addition to the congeniality and liking one another, it’s also the resources.

“We have the patient material that no other center in the world has because this is a rare disease and a rare clinical situation. So we have the clinical material but we don’t have the basic science expertise to answer this type of question.”

It’s the perfect collaboration for him, Einhorn said, because he doesn’t work in the laboratory; he takes care of patients, so his work is on the clinical research side.

Einhorn’s earliest work in the field of testicular cancer is a story that actually has a Grand Rapids dateline.

In 1974, when he was a very young scientific investigator and brand new faculty member at Indiana University, IU researchers had just started doing their first studies of platinum, then an experimental cancer drug.

“I don’t even know why, but we were getting all the testicular cancer patients from Grand Rapids, and we developed a clinical collaboration with Butterworth Hospital and the oncology people who were here at the time,” he recalled.

Because patients didn’t have access to the drug in Grand Rapids and it was a rare disease, Grand Rapids physicians began sending their patients to IU’s School of Medicine. It has since become the go-to institution in terms of patient referrals from around the world and a world resource on the subject of testicular cancer. 

“Certainly, the largest catchment area for us in the 1970s when we first did these studies was Grand Rapids, Michigan.”

The next step in the collaboration is an expanded study, Teh said. Both he and Einhorn expect to get internal review board approval from their respective institutions to launch a larger-scope study in the next two or three months.

The Van Andel Research Institute (VARI) and the Van Andel Institute’s (VAI) board of scientific advisers honored Einhorn, who was in town Thursday, with the 2003 Daniel Nathans Memorial Award for his groundbreaking work in curing testicular cancer.

The VAI established the award in 2000 in memory of Dr. Nathans, who was a founding member of the institute’s scientific board and world-renowned in the field of molecular biology.