Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Finds Gut Microorganisms May Determine Cancer Treatment Outcome

Published: Monday, November 25, 2013
Last Updated: Monday, November 25, 2013
Bookmark and Share
An intact population of microorganisms that derive food and benefit from other organisms living in the intestine is required for optimal response to cancer therapy.

NCI scientists found that tumors of germ-free mice (mice completely lacking these microorganisms), or mice treated with antibiotics to deplete the gut of bacteria, were largely impaired in their ability to respond to immunotherapy that slows cancer growth and prolongs survival. The mice were also impaired in their ability to respond to mainstay chemotherapy drugs such as oxaliplatin and cisplatin. These findings in mice may underscore the importance of microorganisms in optimal cancer treatment outcomes in humans. The study, led by Romina Goldszmid, Ph.D., staff scientist, NCI, and Giorgio Trinchieri, M.D., director of the Cancer and Inflammation Program, Center for Cancer Research, NCI, appeared Nov. 22, 2013, in Science.

Gut commensal microbiota are microorganisms that live in the gut and thrive but do not affect their host, in this case laboratory mice. Humans also harbor gut commensal microbiota that can influence local and body-wide inflammation as well as modify the tumor microenvironment, which consists of cells, signaling molecules and mechanisms that may support tumor growth and also cause drug resistance.

To study the importance of commensal bacteria, the scientists used mice raised in sterile conditions from birth so they did not harbor any bacteria, or alternatively, conventionally raised mice that received a potent antibiotic cocktail that is known to decrease bacteria by more than 10,000–fold.  The mice received these antibiotics in their drinking water, starting three weeks prior to tumor inoculation. They continued to receive doses of the antibiotic cocktail throughout the experiment.

To analyze tumors at comparable stages of progression, lymphoma, colon, and melanoma cancers that could be transplanted were selected, based on their susceptibility to therapeutic drugs. Cancer cells from these tumors were then injected under the skin of the mice, where they formed tumors that grew to reach a diameter of one-fifth of an inch or more. The tumors were then treated with an immunotherapy that included CpG-oligonucleotides, which stimulated the immune system, or with the chemotherapy drugs oxaliplatin and cisplatin, which attacked the tumors.

Germ-free mice, or mice that received the antibiotic cocktail, responded poorly to drug therapy for their tumors. This resulted in a lower production of cytokines (proteins secreted by lymph cells that affects cellular activity and controls inflammation) as well as lower tumor death therefore demonstrating that optimal responses to cancer therapy required an intact commensal microbiota.

In an independent co-submitted study that will appear in the same issue of Science, Laurence Zitvogel, M.D., Ph.D., Gustave Roussy Institute, Paris, and colleagues showed that a different type of chemotherapy drug, cyclophosphamide, altered the composition of the intestinal microbiota and damaged the intestinal wall, thereby affecting optimal anti-tumor immune response and the therapeutic effectiveness of cyclophosphamide.

“The use of antibiotics should be considered as an important element affecting microbiota composition. It has been demonstrated, and our present study has confirmed, that after antibiotic treatment the bacterial composition in the gut never returns to its initial composition,” said Trinchieri. “Thus, our findings raise the possibility that the frequent use of antibiotics during a patient’s lifetime or to treat infections related to cancer and its side-effects may affect the success of anti-cancer therapy.”

In next steps, Goldszmid and Trinchieri will work in mice to fully characterize the molecular signaling by which the bacteria in the gut can actually send messages to distant organs or tumors and change the type and level of inflammation present in those organs. They also plan to characterize, in humans, the role of gut bacteria on the bodies’ inflammatory response and tumor response to therapy. Additionally, the researchers plan to design clinical studies by giving antibiotics to healthy volunteers to study their effect on the molecular mechanisms regulating inflammation.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,500+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
Wednesday, May 25, 2016
Visual Impairment, Blindness Cases in U.S. Expected to Double by 2050
Researchers at NIH have suggested that there is a need for increased screening and interventions to identify and address treatable causes of vision loss.
Friday, May 20, 2016
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Large-scale HIV Vaccine Trial to Launch in South Africa
NIH-funded study will test safety, efficacy of vaccine regimen.
Wednesday, May 18, 2016
New HIV Vaccine Target Discovered
NIH-Led team have discovered a new vaccine target site on HIV.
Tuesday, May 17, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Investigational Malaria Vaccine Protects Healthy U.S. Adults
Researchers at NIH have found that the malaria vaccine protected a small number of healthy, malaria-naïve adults in the U.S. from infection for more than one year after immunization.
Tuesday, May 10, 2016
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Thursday, May 05, 2016
Finding Factors That Protect Against Flu
A clinical trial examining the body’s response to seasonal flu suggests new approaches for evaluating the effectiveness of seasonal flu vaccines.
Wednesday, April 27, 2016
Factors Influencing Influenza Vaccine Effectiveness Uncovered
The long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited, new research suggests.
Thursday, April 21, 2016
Study Finds Factors That May Influence Influenza Vaccine Effectiveness
Researchers at NIH have suggested that the long-held approach to predicting seasonal influenza vaccine effectiveness may need to be revisited.
Wednesday, April 20, 2016
Serotonin Transporter Structure Revealed
Researchers determined the 3-D structure of the serotonin transporter and visualized how two common antidepressants interact with the protein.
Wednesday, April 20, 2016
Improving Flu Vaccine Effectiveness
NIH study finds factors that may influence influenza vaccine effectiveness.
Wednesday, April 20, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Scientific News
The Rise of 3D Cell Culture and in vitro Model Systems for Drug Discovery and Toxicology
An overview of the current technology and the challenges and benefits over 2D cell culture models plus some of the latest advances relating to human health research.
World’s Largest Coral Gene Database
‘Genetic toolkit’ will help shed light on which species survive climate change.
A Boost for Regenerative Medicine
Growing tissues and organs in the lab for transplantation into patients could become easier after scientists discovered an effective way to produce three-dimensional networks of blood vessels, vital for tissue survival yet a current stumbling block in regenerative medicine.
Breast Cancer Drug Hope
A drug for breast cancer that is more effective than existing medicines may be a step closer thanks to new research.
Untangling Disease-Related Protein Misfolding
Work advances understanding of genetic forms of thrombosis, emphysema, cirrhosis of the liver, neurodegenerative diseases and inflammation, among others.
Early Genetic Changes in Premalignant Colorectal Tissue Identified
Findings point to drivers of early cancer development, targets for cancer prevention therapies.
Harnessing Nature’s Vast Array of Venoms for Drug Discovery
Scripps scientists have developed a method for rapidly identifying venoms.
Nanoparticles Target, Transform Fat Tissue
Nanoparticles designed to target white fat and convert it to calorie-burning brown fat slowed weight gain in obese mice without affecting food intake. This proof-of-concept work could lead to new therapies to treat obesity.
New Cancer Fighters Emerge From Lab
Rice University lab simplifies total synthesis of anti-cancer agent.
Scientists Find Evidence That Cancer Can Arise Changes
Researchers at Rockefeller University have found a mutation that affects the proteins that package DNA without changing the DNA itself can cause a rare form of cancer.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!