ZEIGER

Kimmel Cancer Center researcher Christopher Umbricht, M.D., Ph.D., understands the power of translational research. In 2000, he found himself simultaneously a scientist working to understand an enzyme called telomerase and a patient, applying his research to thyroid cancer.

Umbricht and cancer surgeon Martha Zeiger, M.D., had been studying telomerase for several years as a potential biomarker for the detection of certain types of cancer, including breast cancer and thyroid cancer.

In a serendipitous twist of fate, Umbricht was among the early researchers to test telomerase in the lab, and became the first patient at Johns Hopkins to have his tumor tested for this marker.

When a needle biopsy, removing a sampling of cells from a small lump on his neck, revealed a follicular thyroid tumor, he was shocked that his research was now becoming his personal reality.

The treatment of follicular thyroid tumors is a medical challenge. Unlike other tumors that display obvious signs of being either a cancer or a harmless benign tumor, follicular thyroid tumors are not so clear cut. The entire tumor must be removed surgically and examined under a microscope to determine if the tumor is cancer, and until recently, this was done by performing a complete removal of the thyroid gland, requiring lifelong treatment with oral medications to replace the natural hormone. “Without a sure way to know, we could not risk leaving the gland in when it might be cancerous,” says Zeiger.

Yet, the majority of tumors — about 80% — are benign, and would not have required surgery if there was a nonsurgical way to distinguish cancer from noncancer.

If they could figure out a way to identify the cancerous tumors requiring surgery to remove the whole thyroid, they could spare 15,000 people each year unnecessarily invasive surgeries and the need for lifelong medication, she says.

UMBRICHT

The thyroid is a small, butterfly-shaped organ in the front of the neck that performs a mighty job. It produces hormones that are carried throughout the bloodstream to every cell in the body. All of a person’s organs — the heart, brain, liver, kidneys and skin — require the right amount of thyroid hormone to function correctly. Body temperature, cholesterol levels, moods and memory are all affected by the thyroid hormone.

Umbricht was confident enough in their telomerase research that he wanted to use the biomarker to guide his treatment. Zeiger was not convinced.

Despite persuasive laboratory studies on human tumors, the findings had not been used to alter therapy. The use of telomerase as a tumor marker was still in the research phase, and she advised Umbricht to have the surgery.

The cells removed from Umbricht’s tumor during the needle biopsy did not show signs of telomerase, indicating the tumor was benign.

Therefore, Umbricht opted for more limited surgery, removing just the thyroid lobe containing the tumor. Fortunately, the microscopic exam confirmed the absence of cancer tissue.

As the research advanced and technologies improved and they delved deeper into the research, as is often the case with cancer, it proved to be more complicated.

With their ongoing research, the initial success in using the telomerase enzyme to distinguish thyroid cancer from benign thyroid tumors revealed some problems. Their initial biomarker lacked the sensitivity (ability of a test to correctly find disease in the person tested) and specificity (ability of a test to correctly determine the person tested is disease-free) to be a viable cancer test.

The precision medicine goal of directing treatment to the patients who need it and away from those who could be safely spared surgery and lifelong medication remains an important area of research, however, and progress has been made.

Zeiger, Umbricht and collaborators have now shifted their focus to the role of easily detectable genetic mutations in telomerase genes as a more reliable biomarker, and one that seems to mark aggressive tumors that are most likely to spread to other parts of the body. They continue to study the biomarker in samples of follicular thyroid tumors removed during surgery as they work toward a test that could reliably guide therapy.