Through the Lenz

Oncologist Heinz-Josef Lenz has an overriding commitment to better research and treatment for cancer patients.

by Alicia Di Rado

Heinz-Josef Lenz, M.D., stands up for his patients with a passion.

Witness him in action and there can be no doubt of his commitment to those with colorectal, gastric and other abdominal cancers.

There is Lenz, associate professor of medicine and director of USC/Norris’ gastrointestinal oncology program, arguing heatedly with another physician about the proper follow-up for a patient. There again is Lenz, urgently calling a hospital staff member to get his patient’s paperwork cleared up.

And there is Lenz in the USC/Norris lobby, hugging one of his patients who survived cancer, a huge smile breaking across his face.

Perhaps part of the passion comes from the life-changing news he must deliver to patients and their families. He becomes their ultimate advocate, trying to squeeze the greatest benefits medicine can offer to save or improve their lives.

If Lenz has his way, he will have more optimistic news to offer patients in the years ahead. His team moves research from the lab bench to the clinic, seeking to find the best treatments for patients. He also offers the latest types of promising, investigational drugs.

Lenz is the wielder of both embraces and outbursts, a paradox of personalities. Yet his clinical work and research shine some light into the overriding passion that explains it all: his steadfast commitment to better treatment for today’s—and tomorrow’s—cancer patients.

From casks to cancer
Lenz grew up in Abenheim in western Germany’s picturesque Rhine Valley. With a coat of arms dating back to 1520, the Lenz family owns a winery that annually produces hundreds of thousands of liters of Riesling, the wine that made the region’s name.

Despite the success of the family business, Lenz heard the calling of medicine rather than viticulture. After earning a full academic scholarship to attend medical school—a rarity in Germany—he trained at the University Hospital of Tuebingen as a hematologic oncologist.

Then he got an offer he could not refuse. The Mildred Scheel Foundation research fellowship, which fosters training in cancer research, supported Lenz’s move to the Keck School of Medicine in 1991.

With his high-energy demeanor, Lenz quickly was initiated into the world of research at USC. He joined the laboratory team of Peter V. Danenberg, Ph.D., professor of biochemistry and molecular biology at the Keck School, biochemist Kathleen Danenberg, and Larry Leichman, M.D., and Gail Leichman, M.D., gastrointestinal oncologists then at USC/Norris.

Those experiences as a junior researcher united the two sides of academic medicine that still thrill Lenz today: seeing cancer patients in the clinic and reaping scientific advances in the laboratory that promise to help patients further.

As a researcher, Lenz immersed himself into cancer genetics. Over the past decade, he focused his research in several areas:
• How patients’ genes influence how well different chemotherapies fight their particular cancer;
• Whether patients’ genetic makeup causes them to experience more side effects with certain chemotherapies than others;
• How someone’s genetic makeup might heighten the risk of developing cancer; and
• Clinical trials of innovative drugs against cancer.
Although his research projects vary widely, a single thread ties much of the work together: using genetic discoveries to customize treatment and prevention for the needs of each patient.

A personal plan
Peppered amid the 3 billion DNA letters that make up the human genome are a slew of genes important to the birth and quashing of cancer.

These genes can come in different varieties, called polymorphisms, throughout the population, Lenz explains. Polymorphisms account for characteristics that differ from person to person, such as hair or eye color. But most polymorphisms are less physically obvious, such as variations in genes that are associated with cancer.

According to Lenz’s research, certain cancer-related polymorphisms may predict which chemotherapies would help a patient battle cancer and which would make the patient feel sick.

“If physicians could know in advance whether a chemotherapy drug will likely help a patient, that would greatly improve modern cancer treatment,” Lenz explains.
And there lies the potential power of genomic profiling.

Today, oncologists offer a standard, accepted chemotherapy for every patient with a certain type and stage of cancer. While standard therapy has been proven to help many patients, some patients fail therapy. Some may try another approved drug, while some enter clinical trials of investigational drugs. Some go through numerous rounds of different chemotherapies.

But genomic profiling goes beyond the trial-and-error approach. With information on polymorphisms from genomic profiling, oncologists will increasingly be able to pair patients with their ideal chemotherapy, right from the start.

Lenz and his laboratory partners are one of the exclusive teams of researchers worldwide racing to investigate genetic polymorphisms and find relationships between certain polymorphisms and response to chemotherapy.

Among the targets of Lenz’s research are genes that read like a high-tech alphabet soup: the thymidylate synthase, or TS, gene; the excision repair cross-complementing gene 1, known as ERCC1; the X-ray repair cross-complementing gene 1, called XRCC1; and the Xeroderma pigmentosum group D, or XPD gene.

Everyone has a pair of each of these genes, and each of the genes controls the expression of a specific protein important to the human body.

The TS protein is critical to reproducing DNA, while the ERCC1 protein helps repair damaged genetic material in cells. Unfortunately, cancerous tumors also feed off the TS to reproduce their own DNA and use ERCC1 to repair their own DNA after chemotherapy damages it.

Lenz’s group found that patients whose blood showed a certain polymorphism in the TS and ERCC1 genes that cause low TS and ERCC1 expression responded especially well to oxaliplatin, an investigational platinum drug. And that is just one finding from a seemingly constant stream of research from the lab.

Genomic profiling is already making its way to clinical practice in the form of a USC-spinoff diagnostics company called Response Genetics, run by Kathleen Danenberg. USC physicians can send in a slide of a patient’s cancerous tumor, and after molecular analysis, the company provides information about the likelihood that the tumor will respond to a variety of chemotherapies.

Conviction for caring
Lenz brings some of these advances to patients in the clinic at USC/Norris through new investigational drugs. For those advanced colorectal cancer patients with high TS expression, for one, he offers a clinical trial of the drug NB1011, or thymectacin, which has been shown to help.

Lenz often hears about promising drug trials at conferences and meetings and quickly tries to bring unique drugs with potential to patients at USC/Norris. For example, the center is only one of three sites in the nation to offer a clinical trial of an investigational drug called SU11248 for abdominal neuroendocrine cancers, which include carcinoid tumors and pancreatic islet cell tumors. The drug is thought to hamper three different proteins that help cancer cells thrive.

But Lenz thinks beyond new drugs. At the helm of the largest gastrointestinal oncology practice at USC/Norris, Lenz tackles the care of his cancer patients with gusto, and sometimes tears.

“Heinz loves his patients. He knows their stories and knows them personally—he knows them as people, not as cases,” says Yolee Casagrande, R.N., nurse coordinator at the USC/Norris Colorectal Center and Lenz’s longtime colleague.

Casagrande remembers one of Lenz’s patients in particular: a young mother who was raising a little boy single-handedly. “She had a terrible cancer diagnosis, and fought so hard for a year and a half,” she says. “We knew she was dying. He asked if I would come with him to tell her.

“We sat down with this young woman, but Heinz was so heartbroken he couldn’t get the words out. That’s what he’s about.”

That same conviction and passion may contribute to his alter ego: the hard-nosed, opinionated physician who will not shy from drawn-out arguments to get what is needed for his patients. “He’s not a wishy-washy guy,” Casagrande says. “He knows what he wants, and he wants his patients’ care to be the best.

“Isn’t that what everyone wants in their physician?"

For more information about the research of Heinz-Josef Lenz, M.D., or to learn more about any of The Doctors of USC, call
1-800-USC-CARE (1-800-872-2273).