Navigation Links
Solid tumor cells not killed by radiation and chemotherapy become stronger
Date:6/9/2008

DURHAM, N.C. Because of the way solid tumors adapt the body's machinery to bring themselves more oxygen, chemotherapy and radiation may actually make these tumors stronger.

"In a sense, these therapies can make the tumor healthier," said Mark W. Dewhirst, D.V.M., Ph.D., professor of radiation oncology at Duke University Medical Center. "Unless the treatment is very effective in killing many if not most tumor cells, you are shooting yourself in the foot."

Dewhirst and colleagues Yiting Cao, M.D., Ph.D., of Duke Pathology, and Benjamin Moeller, M.D., Ph.D. have introduced this counter-intuitive idea at recent conferences and in a review article featured in the June issue of Nature Reviews Cancer.

Radiation and chemotherapy do kill most solid tumor cells, but in the cells that survive, the therapies drive an increase in a regulatory factor called HIF1 (hypoxia-inducible factor 1), which cells use to get the oxygen they need by increasing blood vessel growth into the tumor. Solid tumors generally have low supplies of oxygen, Dewhirst explained and HIF1 helps them get the oxygen they need.

The review article concludes that blocking HIF1 would provide a clear mechanism for killing solid-tumor cells, particularly cells that are proving resistant to radiation or chemotherapy treatments.

As a part of this work, Dewhirst's team has been studying the phenomenon of rising and falling oxygen levels in tumors, called cycling hypoxia. Oxygen levels have been found to naturally cycle up and down in individual blood vessels as well as large tumor regions. This instability in the tumor's oxygen levels can increase HIF-1 production and cause radiation therapy to fail, Dewhirst said.

"It is my opinion that the whole tumor grows more aggressively because of this pulsation of oxygen at low levels," Dewhirst said. "Most people thought cycling hypoxia was caused by temporary stoppage of blood flow in single blood vessel in tumors. In fact, however, oxygen levels cycle up and down virtually everywhere in the tumor, which is caused by fluctuations in blood flow rate. It has been a challenge to convince people of this."

Dewhirst and colleagues have made movies of oxygen transport in a tumor of a living animal that show the oxygen levels cycle up and down significantly, pulsing in waves seen as color changes in the movies. (View these movies at the Nature Reviews Cancer site: http://www.nature.com/nrc/journal/v8/n6/suppinfo/nrc2397.html )

The Duke team argues that blocking HIF1 is the consistent answer to tumor growth problems. Blocking HIF1 activity interferes with the tumor's ability to undergo glycolysis (energy production) in low-oxygen conditions, which blocks tumor growth, the authors wrote. Exactly how to accomplish chemotherapy or radiation treatment in the safest, most effective ways, in combination with HIF1 blockade, is still open for exploration, Dewhirst said.

For example, targeting HIF1 in the early stages of tumor growth, especially in very early cancer spread, may help, Dewhirst said. "For a woman who has had a primary breast tumor removed, and who is at high risk for cancer spread, this might be a situation in which you'd target HIF1," he explained. "Blocking HIF1 makes sense during the early stages of angiogenesis, which is the accelerated phase of blood vessel formation. In this way, you could keep the early metastasis sites inactive and prevent them from growing."

The Duke team has completed a phase I trial with a HIF1 inhibitor. "We are actively pursuing this clinically and will be moving this study into Phase 2," Dewhirst said. "We are interested in other applications of HIF-1 inhibition in combination with radiation and chemotherapy for different diseases."


'/>"/>

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related medicine news :

1. MedAmerica Reports Solid Growth, Outperforms Industry
2. Insurance Department to Hold Statewide Meetings on Proposed Consolidation of Independence Blue Cross, Highmark
3. STAAR Surgical Reports Solid First Quarter Progress
4. Life Sciences Discovery Fund Awards $2.2 Million to Support New Solid-Tumor Research Program
5. A long-term survival offered by resection of solid-pseudopapillary tumor of the pancreas?
6. New target for cancer therapy may improve treatment for solid tumors
7. Novo Nordisk Consolidates U.S. Diabetes Sales Leadership Under Single Vice President
8. Triple-S Management Corporation Reports Record Consolidated Operating Income, Net Income and EPS for 2007
9. SAFC Pharma Expands Its Pharmorphix Solid State Chemistry Services
10. Insurance Department Will Hold Public Hearings on Proposed Consolidation of Highmark, Independence Blue Cross
11. James E. Harris to Become Chief Financial Officer of Coca-Cola Bottling Co. Consolidated
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/18/2017)... ... August 18, 2017 , ... Rollon Skin ... anti-aging skincare solutions, recently announced the launch of two new skincare products, ... yet effective alternative to expensive plastic surgery or in-patient cosmetic dermatological procedures. , ...
(Date:8/17/2017)... ... August 17, 2017 , ... Riccobene Associates Family Dentistry, the ... NC to its family of practices. Residents of Goldsboro will be able to ... 2017. , Riccobene Associates Family Dentistry, founded by Dr. Michael Riccobene in ...
(Date:8/17/2017)... , ... August 17, 2017 , ... ... a period of three years for its residential drug and alcohol detox program. ... to an organization and shows the organization’s substantial conformance to the CARF standards. ...
(Date:8/17/2017)... Lansdale, PA (PRWEB) , ... August 17, 2017 ... ... Reverse Expo is an opportunity for IDNs and healthcare systems to interact with ... of Hayes, Inc. and Karla Barber, RN, BCN, CVAHP, System Director of Clinical ...
(Date:8/17/2017)... , ... August 17, 2017 , ... ... (ER) on Wednesday, August 16, to community partners. The newly renovated ER was ... Track” area for minor emergencies, eight semi-private rooms to deliver patient results, improve ...
Breaking Medicine News(10 mins):
(Date:8/15/2017)... Aug. 15, 2017  Axium Pharmaceuticals Inc., the creator of the drug ... in the beginning stages of an IPO. The ... with the average cost of a prescription epilepsy drug being $450.00-$1200.00 for ... AXIUM PHARMACEUTICALS, INC ... Another staggering figure is the fact that Americans spent ...
(Date:8/11/2017)... Israel , Aug. 11, 2017 DarioHealth ... with mobile health and big data solutions, today announced ... on Monday, August 14 and host a conference call ... quarter 2017 operating and financial results and its strategy ... will be hosted by Erez Raphael , Chief ...
(Date:8/7/2017)... Aug. 7, 2017 Insightin Health, provider ... retention, and engagement, announced the selection of ... Product Development, effective as of February 2017. In this ... implementation strategy for our clients. Wood brings with ... consulting and business analytics within the healthcare industry. ...
Breaking Medicine Technology: