Navigation Links
Breast cancer cells recycle to escape death by hormonal therapy
Date:10/2/2008

Many breast cancer cells facing potentially lethal antiestrogen therapy recycle to survive, researchers say.

About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.

"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.

One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in Nrenberg, Germany.

It's called macroautophagy autophagy means "self eating" and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."

Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.

In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.

"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.

She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.

During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.

A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.

"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.

Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.


'/>"/>

Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

Related biology news :

1. The dietary supplement genistein can undermine breast cancer treatment
2. Breast cancer treatment resistance linked to signaling pathway
3. Expanding cell girth indicates seriousness of breast cancer
4. Stem cells may solve mystery of early pregnancy breast cancer protection
5. Vaccine against HER2-positive breast cancer offers complete protection in lab
6. 31st Annual San Antonio Breast Cancer Symposium
7. Growth factor predicts poor outcome in breast cancer
8. CSHL scientists identify new drug target against virulent type of breast cancer
9. Codeine not safe for all breastfeeding moms and their babies
10. New breastfeeding study shows most moms quit early
11. Foods high in conjugated linoleic acids can enrich breast milk
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Breast cancer cells recycle to escape death by hormonal therapy
(Date:6/15/2016)... June 15, 2016 Transparency ... titled "Gesture Recognition Market by Application Market - Global Industry Analysis ... 2024". According to the report, the  global gesture recognition ... 2015 and is estimated to grow at a ... by 2024.  Increasing application of gesture ...
(Date:6/9/2016)... TURKU, Finland , June 9, 2016 ... French National Police deploy Teleste,s video security solution to ensure ... France during the major tournament ... and data communications systems and services, announced today that its ... Police Prefecture to back up public safety across ...
(Date:6/3/2016)... 2016 Das DOTM ... Nepal hat ein 44 Millionen ... Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, an ... und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte internationale ... teilgenommen, aber Decatur wurde als konformste und ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... MA (PRWEB) , ... June 23, 2016 , ... ... Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute ... platform of microbial tests introduced last year,” stated Bob Salter, Vice President of ...
(Date:6/23/2016)... -- The Biodesign Challenge (BDC), a university competition that asks ... systems and biotechnology, announced its winning teams at the ... York City . The teams, chosen ... MoMA,s Celeste Bartos Theater during the daylong summit. Keynote ... of architecture and design, and Suzanne Lee , ...
(Date:6/23/2016)... ... , ... Supplyframe, the Industry Network for electronics hardware design ... Located in Pasadena, Calif., the Design Lab’s mission is to bring together inventors ... and brought to market. , The Design Lab is Supplyframe’s physical representation of ...
(Date:6/23/2016)... ... June 23, 2016 , ... In a new case report ... detail how a patient who developed lymphedema after being treated for breast cancer benefitted ... change the paradigm for dealing with this debilitating, frequent side effect of cancer treatment. ...
Breaking Biology Technology: