Versatile immunosuppressant drug may have new role in radiotherapy for cancer

November 21, 2002

Frankfurt, Germany: US researchers have discovered that rapamycin[1], a drug developed as an immunosuppressant and now being used in cardiovascular stents[2] and also being tested as a chemotherapy agent to prevent tumour cell proliferation, may have yet another role - enhancing the effectiveness of radiotherapy for cancer patients.

Research in mice at the Mayo Clinic in Rochester, Minnesota, has shown that rapamycin boosts the therapeutic effect of radiation by delaying the regrowth of brain tumours after treatment.

Their findings are being presented at the EORTC-NCI-AACR[3] Symposium on Molecular Targets and Cancer Therapeutics, in Frankfurt, Germany.

Lead investigator Dr Jann Sarkaria, assistant professor and consultant in the clinic's Department of Oncology, told a news briefing today (Thursday 21 November) that combined rapamycin and radiation treatment delayed regrowth of glioblastoma multiforme (GBM)[4] human tumours in mice for an average 19 days compared to treatment with rapamycin alone. In contrast, radiation treatment alone or rapamycin alone had no effect on tumour growth compared to control treatment.

Rapamycin inhibits the activity of a protein, mTOR, which functions in a signalling pathway to promote tumour growth. Rapamycin binds to a receptor protein (FKBP12) and the rapamycin/FKB12 complex then binds to mTOR and prevents interaction of mTOR with target proteins in this signalling pathway.

"It's already known that rapamycin specifically inhibits mTOR and that mTOR is important in regulating cell growth and proliferation. Many GBM tumours have genetic changes that hyperactivate mTOR signalling, and these are the tumours most likely to respond to rapamycin therapy," said Dr Sarkaria.

"But, the exciting finding from our study is that this is the first evidence that mTOR is involved in the cellular response to radiation. It's not clear yet how it works but we think rapamycin slows tumour proliferation during radiation treatment. Similar to its effects with radiation, rapamycin may also enhance the effectiveness of chemotherapies. We already have preliminary data in mice to suggest that rapamycin can enhance the efficacy of one chemotherapy agent in GBM tumours. Moreover, it's possible that the combination of rapamycin with either radiation or chemotherapy might enhance the effectiveness of treatment in other types of cancers, in particular lung and prostate cancer."

The research team is now planning clinical trials looking at the combination of radiation and a rapamycin analogue in GBM and in lung cancer, and other researchers at the Mayo Clinic are evaluating rapamycin in phase I and II trials as a single agent for recurrent GBM.

Dr Sarkaria said that the doses of rapamycin and radiation in the animal studies were realistic approximations of what is used clinically. "Rapamycin is a highly targeted drug that we think inhibits only mTOR. Rapamycin analogues are well tolerated in patients and, unlike the standard chemotherapy agents commonly combined with radiation, we think it is less likely that they will significantly increase the toxicity of radiation."

He concluded: "It is too early to say how significant this finding is. Although the majority of patients presumably will not benefit from this specific combination, it is possible a small subset will. In the long term, the goal of molecular medicine is to custom-tailor treatments to the genetic make-up of individual patients and their tumours. So, if we can identify which patients are likely to respond to this specific combination, then we can treat just those patients who are most likely to benefit from the combination treatment and use alternative treatments for other patients."
[1] Rapamycin: Rapamycin (Sirolimus) is an antibiotic that was isolated over 25 years ago from a strain of fungus found in a soil sample in the Easter Islands. It is used clinically as an immunosuppressant to prevent organ rejection in kidney patients in combination with other drugs e.g. corticosteroids.

[2] Rapamycin use in cardiovascular stents: the drug is used to prevent coronary arteries re-narrowing after angioplasty - a method of treating blockage or narrowing of blood vessels by inserting a balloon into the constriction to reopen it.

[3] EORTC [European Organisation for Research and Treatment of Cancer]; NCI [National Cancer Institute]; AACR [American Association for Cancer Research].

[4] Glioblastoma Multiforme (GBM): The most common and aggressive of the primary brain tumours. It is highly malignant and infiltrates the brain extensively. Surgical resection followed by radiation is the standard of care. However, this aggressive tumour is incurable and the overall prognosis has changed little in the past two decades despite major improvements in neuroimaging, neurosurgery and radiotherapy.

Further information:
Margaret Willson (media information officer)
Tel: 44-153-677-2181
Fax: 44-153-677-2191
Mobile: 44-797-385-3347

From: 16:00hrs CET Monday 18 November to 17:00hrs CET Friday 22 November
EORTC-NCI-AACR symposium press office:
Tel: 49-697-5757-3294
Fax: 49-697-5757-3451

European Organisation for Research and Treatment of Cancer

Related Chemotherapy Articles from Brightsurf:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.

Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.

Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

Male fertility after chemotherapy: New questions raised
Professor Delb├Ęs, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.

Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.

Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.

Read More: Chemotherapy News and Chemotherapy Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to