Navigation Links
Secrets of cellular signaling shed light on new cancer stem cell therapies
Date:4/9/2008

ANN ARBOR, Mich.---By revealing the inner workings of a common cell-to-cell signaling system, University of Michigan biologists have uncovered new clues about mysterious and contentious creatures called cancer stem cells.

The findings also have implications for a high-profile breast-cancer drug trial getting underway at the U-M Medical School and two other institutions.

In the groundbreaking trial, researchers are combining chemotherapy with a drug that blocks the Notch signaling pathway, which helps regulate fetal development and is active in most organ systems throughout a person's life.

The aim is to use so-called Notch inhibitors to attack cancer stem cells, the small fraction of stem cells inside a tumor that help it survive and that fuel its growth.

But a big concern is that the Notch inhibitors, while helping to destroy cancer stem cells, might also kill or harm the normal, healthy stem cells critical to a patient's survival such as blood-forming stem cells in the bone marrow.

New results from the U-M's Dr. Ivan Maillard and his colleagues may allay some of those fears. The researchers showed that blood-forming stem cells in mice survive just fine when the Notch signaling pathway is experimentally blocked.

"Our data indicate that normal blood-forming stem cells should not be damaged by the Notch inhibitor drug being used in these patients," said Maillard, a hematologist and a Life Sciences Institute researcher.

"That's important, since these patients typically need good blood stem cells to maintain their blood counts and recover from the effects of chemotherapy," he said.

The Notch findings will be published Thursday in the journal Cell Stem Cell. Maillard's team includes researchers from the University of Pennsylvania School of Medicine, the Swiss Institute for Experimental Cancer Research, and Harvard Medical School.

Dr. Max Wicha, director of the U-M Comprehensive Cancer Center, said Maillard's results are welcome news for cancer stem cell researchers, and for the 30-patient metastatic breast-cancer drug trial that launched last month at his center, at the Baylor College of Medicine in Houston, and at the Dana-Farber Cancer Institute in Boston.

"It's really important, because a lot of what we're thinking about now, therapeutically, is trying to find ways to attack these cancer stem cells, because we think that's really what drives the malignancies," said Wicha, who was not involved in the Notch study.

"Ivan's paper, combined with our own work, shows that there may be differences between normal stem cells and cancer stem cells, and perhaps those differences can be exploited therapeutically," Wicha said.

The cancer stem cell theory is controversial. Some researchers are not convinced that cancer stem cells exist.

The current two-stage drug trial uses a Notch inhibitor originally developed by Merck for Alzheimer's patients in the late 1990s, followed by chemotherapy. The intent is to use the Notch inhibitor to make cancer stem cells sensitive to the chemotherapy---a one-two punch to knock out tumors.

If the treatment is effective, the results could help sway some cancer-stem-cell skeptics.

The Notch pathway sends signals from a cell's surface membrane into its nucleus. Those signals activate genes that instruct the cell to make proteins that perform various tasks.

In the lab, Maillard and his colleagues were able to prevent Notch signals from activating mouse target genes using two independent techniques.

Many scientists have long assumed that blood-forming stem cells need Notch signals to function properly. But Maillard's team found that the signals are not required for the maintenance of blood-forming stem cells in adult mice.


'/>"/>

Contact: Jim Erickson
ericksn@umich.edu
734-647-1842
University of Michigan
Source:Eurekalert

Related medicine news :

1. Scientists Probe Sepsis Deadly Secrets
2. The Well Life Center in Mesa Unveils The 10 Healing Secrets to Health & Longevity Lecture. Proceeds Benefit The Arizona Special Olympics
3. UPCARE Technology to Share the Secrets of its Parents Success in Lab Outreach
4. Mathematicians help unlock secrets of the immune system
5. New Survey Uncovers Dirty Little Secrets About Americas Oral Care Habits
6. The Well Life Center in Mesa Continues The 10 Healing Secrets to Health & Longevity Lecture. Proceeds Benefit The Arizona Special Olympics
7. Secrets to Long-Lasting Marriages Revealed in Senior Survey
8. Oscar Makeover CHEAT Secrets of the Stars Revealed
9. HealthBarn(R) USA Founder Shares Secrets For Healthy Eating With Rachael Ray
10. Dr. Rovenia Brock Brings Secrets of Living Healthy to Susan G. Komen for the Cure(R)s Circle of Promise
11. Story ideas from molecular & cellular proteomics
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... ... 11, 2016 , ... Life is known for throwing curves. It’s thrown quite ... gather once a year to play softball to raise money through Sun Health ... than 50 players who competed in this year’s softball tournament share a history of ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... their ongoing community involvement program, introduces a new charity campaign to raise funds ... are now being accepted at https://donate.rmhc.org/ . , Ronald McDonald House (RMH) ...
(Date:2/11/2016)... ... 2016 , ... From March 4 through 6, Hidrex ... at the Walter E. Washington Convention Center in Washington, D.C. , At the ... hyperhidrosis (excessive sweating) and its treatment options. Specifically, the company will be talking ...
(Date:2/11/2016)... Ore. (PRWEB) , ... February 11, 2016 , ... ... Medicaid coverage results in significantly higher rates of several common cancer screenings, especially ... resulting in better outcomes and survival rates. , The study,“What Does Medicaid ...
(Date:2/10/2016)... ... ... Early this week, Team Iconic at J. Walter Thompson and Nestlé KITKAT ... global confectionery brand sourced from 100% sustainable cocoa. , The Nestlé Cocoa Plan aims ... activities that focus on better farming, better lives and better cocoa. In order to ...
Breaking Medicine News(10 mins):
(Date:2/10/2016)... Genomic Health, Inc. (Nasdaq: GHDX ) today reported financial ... 31, 2015. --> --> Revenue ... $69.1 million in the fourth quarter of 2014, an increase of ... compared with the same period in the prior year. ... in the fourth quarter of 2015, an increase of 9 percent ...
(Date:2/10/2016)... HERTFORDSHIRE, England och ... -- Erbjudandet lämnas inte, och detta ... eller indirekt, i eller till, och inga ... uppdrag av aktieägare i, något land där ... av accept av Erbjudandet skulle strida mot ...
(Date:2/10/2016)... Mylan N.V. (NASDAQ, TASE: MYL) today announced ... December 31, 2015. --> --> ... revenues of $9.45 billion, up 28% on a constant ... of $9.43 billion. Excluding the impact of the acquisition ... generics business (the "EPD Business"), full year adjusted total ...
Breaking Medicine Technology: