• 11/9/2004
  • Liz Szabo
  • USA Today

Supreme Court Chief Justice William Rehnquist’s diagnosis of thyroid cancer, announced late last month, comes at an time when research in the malignancy — which experts say was stalled for many years — is suddenly taking off.

In the past year or so, scientists have initiated at least 10 new studies of thyroid cancer, and a dozen more will soon be up and running, says Steven Sherman, an associate professor at M.D. Anderson Cancer Center in Houston.

“There’s been an explosion,” Sherman says. “Before that, there was almost nothing.”

Thyroid cancer research has suffered partly because its most common variety is usually curable, making the disease seem less threatening. Yet the most aggressive form of thyroid cancer, anaplastic carcinoma, is one of the most lethal of all tumors. Anaplastic cancers afflict so few people — just a few hundred a year — that experts long doubted that it was possible to even start clinical trials, says Manisha Shah, a thyroid cancer specialist at Ohio State University Comprehensive Cancer Center.

Recent research has been sparked by the discovery of genetic mutations involved in thyroid tumors, as well as progress in the growing field of “targeted” cancer therapies that affect the tumors but not the surrounding, healthy tissue.

Last year, a team of scientists at Johns Hopkins University School of Medicine discovered a genetic mutation that is present in most papillary thyroid cancers, the most common sort. Earlier this year, the same team showed that the mutation is found in about half of anaplastic carcinomas, as well.

The gene, called BRAF, acts as an on/off switch for cell growth. In tumors with the mutation, this switch gets stuck in the “on” position. Almost all thyroid cancers have a mutation in the same growth pathway as this gene, says David Sidransky, director of head and neck cancer research at Johns Hopkins. A group of doctors around the country are testing an experimental drug, known only as BAY 43-9006, that may be able to turn off that switch.

“If this becomes effective in anaplastic, it would be like a dream come true,” Shah says. “You could have a simple pill to fight against this huge monster.”

Although Rehnquist, 80, has not disclosed which type of thyroid cancer he has, experts say that his age and details of his treatment — a tracheotomy, chemotherapy and radiation — suggest his tumor may be anaplastic.

Better treatments for anaplastic cancers are desperately needed, says Scot Remick, a thyroid cancer expert at Case Comprehensive Cancer and the University Hospitals of Cleveland. Survival for patients with anaplastic tumors has improved little in the past 40 years. Although chemo and radiation can shrink anaplastic tumors and buy patients time, they offer only temporary relief. These tumors can triple in size in just days, and patients typically die in two to six months.

“It can grow right before your eyes,” Remick says.

Researchers “stumbled across” one promising treatment for anaplastic disease almost by accident, Remick says. The drug, combretastatin, works by destroying blood vessels that feed tumors. In 1999, researchers tested the medication on patients with different cancers, not even sure of a safe dose. They were amazed when a man named Clayton Twigg saw his anaplastic tumor disappear. Five years later, Twigg is 62 and considered cured. To Remick, Twigg is a “miracle case.” But doctors can’t explain why Twigg responded so well, or if combretastatin will help others, Remick says. The drug also can cause serious side effects, including heart problems.

Doctors such as Shah are testing the popular arthritis drug Celebrex, which also blocks the growth of new tumor blood vessels. Researchers haven’t done enough tests to tell whether the drug will work for large numbers of patients. But in one woman whose papillary cancer had spread to other organs — Ellen Yingst of Springfield, Ohio — Celebrex helped to shrink a tumor in her lung by 40%.

“I guess you just grasp at straws,” says Yingst, whose cancer, first diagnosed 20 years ago, also spread to her brain. “I didn’t have any other options.”

Other therapies aim to make other thyroid cancers more responsive to treatment with radioactive iodine.

Another discovery involves a class of drugs that blocks enzymes called histone deacetylases, which scientists have only recently linked to thyroid cancer, says Richard Robbins, chief of endocrinology at Memorial Sloan-Kettering Cancer Center. These enzymes, which strip protective coatings away from DNA, are hyperactive in cancer cells.

Shah sees even such intermediary studies as a great step forward. Only a few years ago, she says, there were no large treatment trials in thyroid cancer at all. “This is really a prime time,” Shah says. “We’re entering a new era.”