Estimated read time: 4-5 minutes
This archived news story is available only for your personal, non-commercial use. Information in the story may be outdated or superseded by additional information. Reading or replaying the story in its archived form does not constitute a republication of the story.
[STK]
[IN] HEA MTC
[SU] TRI CHI
TO HEALTH, MEDICAL, AND NATIONAL EDITORS:
Adult cancer drugs show promise against an aggressive childhood brain
tumor
MEMPHIS, Tenn., March 27, 2014 /PRNewswire-USNewswire/ -- 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.
Marie Morfouace, Ph.D., a postdoctoral fellow in Roussel's laboratory,
is the study's first author. The other authors are Anang Shelat, Megan
Jacus, Burgess Freeman III, David Turner, Sarah Robinson, Frederique
Zindy, Yong-Dong Wang, David Finkelstein, Giles Robinson, R. Kiplin
Guy and Clinton Stewart, all of St. Jude; Olivier Ayrault and Laure
Bihannic, Institut Curie, Orsay, France; Stephanie Puget,
Necker-Children Hospital, Paris, France; Xiao-Nan Li, Baylor College
of Medicine, Houston; and James Olson, Fred Hutchinson Cancer Center,
Seattle.
The research was funded in part by grants (CA096832, CA155360,
CA114567, CA021765) from the National Institutes of Health; the French
National Cancer Institute; CNRS; Institut Curie; Necker Hospital; the
V Foundation and ALSAC.
SOURCE St. Jude Children's Research Hospital
-0- 03/27/2014
/CONTACT: St. Jude Media Relations: Carrie Strehlau, (desk) (901) 595-2295, (cell) (901) 297-9875, carrie.strehlau@stjude.org ; or Summer Freeman, (desk) (901) 595-3061, (cell) (901) 297-9861, summer.freeman@stjude.org
/Web Site: http://www.stjude.org
CO: St. Jude Children's Research Hospital
ST: Tennessee
IN: HEA MTC
SU: TRI CHI
PRN
-- DC92437 --
0000 03/27/2014 16:21:00 EDT http://www.prnewswire.com
Copyright © The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
