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:6/26/2016)... North Carolina (PRWEB) , ... June 26, 2016 , ... ... release of a new product that was developed to enhance the health of felines. ... for centuries. , The two main herbs in the PawPaws Cat Kidney Support ...
(Date:6/25/2016)... ... June 25, 2016 , ... Austin residents seeking Mohs surgery services, can now ... and to Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings ... The selective fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under the ...
(Date:6/25/2016)... Long Beach, CA (PRWEB) , ... June 25, 2016 , ... ... from UCLA with Magna Cum Laude and his M.D from the David Geffen School ... San Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at ...
(Date:6/24/2016)... CA (PRWEB) , ... June 24, 2016 , ... A ... procedures that most people are unfamiliar with. The article goes on to state that ... but also many of these less common operations such as calf and cheek reduction. ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Scientific Sessions in Dallas that it will receive two significant new grants to ... came as PHA marked its 25th anniversary by recognizing patients, medical professionals and ...
Breaking Medicine News(10 mins):
(Date:6/26/2016)... 26, 2016 One of Australia,s ... formation of a new biotechnology company, Noxopharm Limited [ABN 50 608 ... IPO and to list on the ASX. Noxopharm is ... to enter a Phase 1 clinical study later this year. ... one of the biggest problems facing cancer patients - the ability ...
(Date:6/26/2016)... 27, 2016 Jazz Pharmaceuticals plc (Nasdaq: ... the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended ... Pharmaceuticals, Inc. ("Celator"; Nasdaq: CPXX ) expired ... Time). As previously announced on May 31, ... merger agreement under which Jazz Pharmaceuticals has commenced a ...
(Date:6/26/2016)... , June 27, 2016  VMS Rehab Systems, Inc. ... will take whatever measures required to build a strong ... which is currently listed on the OTC Markets-pink current ... Chairman and CEO, "We are seeing an anomaly in ... understand, not only by the Company, but shareholders and ...
Breaking Medicine Technology: