Transplant drug could improve success of cancer radiation therapy

Friday, November 22nd 2002, 12:00 am

By: News On 6

FRANKFURT, Germany (AP) _ Researchers have discovered that a drug normally used to prevent the rejection of kidney transplants might improve radiation therapy by keeping cancer tumors from growing between doses.

Radiotherapy kills tumor cells, but one of the hurdles to the treatment, which is given as a course of intermittent doses, is that the cancer cells that survive the onslaught continue to multiply between sessions.

Preliminary research presented Thursday at a meeting of U.S. and European cancer experts found that when mice grafted with human brain tumors got the transplant drug rapamycin during radiotherapy, their cancer did not grow as much in the breaks between radiation doses.

The mice were given glioblastoma multiforme, the most deadly form of brain cancer.

Over the last few years scientists have learned that, for several types of cancer, giving radiotherapy and chemotherapy drugs at the same time improves by about 30 percent the ability to stop tumors spreading and enables cancer patients to live 10 percent longer compared with giving the two treatments sequentially.

``This has not been seen in brain tumors so far,'' said Dr. Harry Bartelink, head of radiotherapy at the Netherlands Cancer Institute in Amsterdam, who was not involved in the study. ``In these types of brain tumors, radiotherapy and chemotherapy have been extremely ineffective. Nearly all patients will die.''

``If you can translate these laboratory findings to the clinic and improve the efficacy of radiotherapy, that would be a major step forward,'' Bartelink said.

Rapamycin, also known as Rapamune, is traditionally used to suppress the immune system and prevent rejection in kidney transplant patients. Scientists now know that it works by blocking the switching on of the immune cells responsible for attacking the transplant.

They recently discovered that rapamycin also appears to attack cancer, at least in cells in the lab and in animals.

It turns out that the drug blocks a protein, called mTOR, which regulates many activities involved in the life cycle of cells. Many common types of cancer involve genetic abnormalities that affect how mTOR operates.

``The exciting finding from our study is that this is the first evidence that mTOR is involved in the cellular response to radiation,'' said Dr. Jann Sarkaria, a Mayo Clinic oncology professor who conducted the study. ``It's not clear yet how it works, but we think rapamycin slows tumor proliferation during radiation treatment.''

In the study, the mice got three doses of radiation over 18 days _ one dose every six days. They were also given rapamycin injections regularly throughout the 18 days.

The size of their tumors, which had been implanted just under the skin, were measured over the course of the study.

``Where they got sham radiation and (fake) injections, the tumors grew quite quickly. Likewise, with radiation only and with rapamycin alone,'' Sarkaria said. ``With the combination of rapamycin plus radiation, it took quite a bit longer for these tumors to regrow to three times their original volume.''

Sarkaria said he plans next to test rapamycin combined with radiotherapy in patients with brain and lung cancers.

The symposium, which focuses on so-called targeted cancer therapies, is held annually by the European Organization for Research and Treatment of Cancer, the U.S. National Cancer Institute and the American Association for Cancer Research.