Navigation Links
Adult cancer drugs show promise against an aggressive childhood brain tumor

(MEMPHIS, Tenn. March 27, 2014) The quest to improve survival of children with a high-risk brain tumor has led St. Jude Children's Research Hospital investigators to two drugs already used to treat adults with breast, pancreatic, lung and other cancers. The study was published today online ahead of print in the journal Cancer Cell.

Researchers demonstrated that the drugs pemetrexed and gemcitabine killed cells from mouse and human brain tumors, called group 3 medulloblastoma, growing in the laboratory. Medulloblastoma is diagnosed in about 400 children annually in the U.S., making it the most common pediatric brain tumor. Of the four distinct medulloblastoma subtypes, patients with group 3 medulloblastoma have the worst prognosis.

Used together, pemetrexed and gemcitabine doubled life expectancy of mice with human group 3 medulloblastoma, compared to untreated mice. When pemetrexed and gemcitabine were combined with two chemotherapy drugs currently used to treat pediatric medulloblastoma, the mice lived even longer.

The drugs were identified by screening the St. Jude library of 7,389 compounds looking for ones that targeted group 3 mouse tumor cells rather than normal mouse brain cells. The library included all 830 drugs U.S. Food and Drug Administration (FDA) approval. Pemetrexed and gemcitabine emerged as the top candidates, based in part on their ability to kill group 3 medulloblastoma tumor cells at concentrations that researchers showed were safe and achievable in patients.

"Our focus was to identify drugs that we could move quickly from the laboratory to the clinic where new chemotherapy options are desperately needed for these high-risk medulloblastoma patients," said the study's corresponding author Martine Roussel, Ph.D., a member of the St. Jude Department of Tumor Cell Biology. "As a basic scientist, it is exciting to be able to translate a laboratory discovery into drugs that are now being used in a clinical trial."

Based on results from this and previous studies, pemetrexed and gemcitabine were included in a St. Jude-led multicenter clinical trial of children and adolescents newly diagnosed with medulloblastoma. The drugs are already approved for treatment of patients with advanced breast cancer as well as ovarian, pancreatic and certain lung cancers. No safety concerns were identified in previous studies of pemetrexed and gemcitabine for treatment in children with other cancers.

Most group 3 medulloblastoma tumors feature excessive levels of the c-MYC protein, which helps to regulate cell growth. The protein is overexpressed in many cancers and is associated with a poor outcome. About 40 percent of patients with c-MYC overexpression and other characteristics of group 3 medulloblastoma become long-term survivors, compared to 80 percent of other medulloblastoma patients.

"The drugs identified in this study will hopefully close that survival gap and improve cure rates for children with group 3 medulloblastoma," said co-author Amar Gajjar, M.D., St. Jude Department of Oncology co-chair.

For this study, researchers relied on mice with group 3 medulloblastoma grown from patient tumors. The mice were developed in Roussel's laboratory and are a powerful tool for testing the effectiveness of drugs against human tumors. Researchers used the mice to show that pemetrexed and gemcitabine worked against human group 3 tumors and that the drugs could be used in combination with existing chemotherapy agents to boost treatment effectiveness without undue risk. Cisplatin and cyclophosphamide were the other drugs used in this study.

"The finding provides a strong rationale for combination therapy with pemetrexed and gemcitabine for treatment of group 3 medulloblastoma," Roussel said. Researchers found no evidence that mouse tumor cells develop resistance to the drugs.

Pemetrexed works by disrupting the ability of cancer cells to proliferate. Gemcitabine kills cells by triggering their suicide pathway. Researchers also found evidence the drugs work specifically against group 3 medulloblastoma. The drugs did not extend survival of mice with a different medulloblastoma subtype.

The study builds on previous St. Jude research that has helped to revolutionize understanding of the origins of medulloblastoma and laid the foundation for a new era of risk-based therapy. The goal is to maximize the likelihood of a cure and minimize long-term side effects. The approach combines clinical factors and the molecular markers associated with the different medulloblastoma subtypes to guide how radiation and chemotherapy are combined with surgery.


Contact: Carrie Strehlau
St. Jude Children's Research Hospital

Related medicine news :

1. Infection Might Raise Blood Clot Risk for Older Adults: Study
2. EKG Heart Test May Predict Risk in Older Adults
3. Unique approach needed to accurately assess health of young adult cancer survivors
4. Out-of-hand tree nut consumption associated with better diet quality in children and adults
5. Symptomatic behaviour in childhood strongly predicts psychiatric treatment as a young adult
6. Gay Adults Rejected by Parents Have Worse Health, Study Finds
7. Feelings of immaturity accompany alcohol misuse into adulthood; discovery could improve treatments
8. Callahan honored for improving older adults health in their doctors offices
9. Anti-tobacco TV ads help adults stop smoking, study finds
10. Childhood Obesity May Raise Odds of Adult Liver Cancer
11. Better health in adulthood starts with early prevention in childhood
Post Your Comments:
(Date:11/28/2015)... ... November 28, 2015 , ... Trying to relax on a couch can actually ... conceived of this design due to personal experience with a bad back," he said. ... and convenience, as well as increases support. It also makes it easier to eat, ...
(Date:11/28/2015)... Viejo, CA (PRWEB) , ... November 28, 2015 , ... ... new fully customizable media panels to choose from, the possibilities are endless. Users have ... and more. With the ProPanel: Pulse masking effects, users are sure to get heads ...
(Date:11/27/2015)... CA (PRWEB) , ... November 27, 2015 , ... According ... at the recent 2015 American Dental Association meeting in Washington D.C. revolved around the ... protect a patient’s overall health. The talk stressed the link between periodontal disease (more ...
(Date:11/27/2015)... ... November 27, 2015 , ... According to an article published November ... they are handling security in light of the recent terrorist attacks in Paris, other ... to stop an attack from reaching U.S. soil. Especially around special events that may ...
(Date:11/27/2015)... ... November 27, 2015 , ... A team of Swiss doctors ... treat it. Surviving Mesothelioma has just posted the findings on the website. Click ... analyzed the cases of 136 mesothelioma patients who were treated with chemotherapy followed by ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... Research and Markets ( ) has announced ... Outlook to 2019 - Rise in Cardiac Disorders and Growing ... to their offering. Boston ... scientific and others. --> The market ... Boston scientific and others. ...
(Date:11/26/2015)... , November 26, 2015 ... the addition of the  "2016 Future ... Global Cell Surface Testing Market: Supplier ... to their offering.  --> ... of the  "2016 Future Horizons and ...
(Date:11/26/2015)... , November 26, 2015 ... the addition of the  "2016 Future ... European Therapeutic Drug Monitoring (TDM) Market: ... Intelligence, Emerging Opportunities"  report to their ... has announced the addition of the  ...
Breaking Medicine Technology: