JAN 11, 2017 02:19 PM PST

Genetic Tweaks Transform Salmonella into Tumor Destroyers

WRITTEN BY: Xuan Pham

Salmonella, the bacteria that is bane of all restaurants and grocery stores, has now been transformed into “tumor-seeking missiles” to help fight one of the most lethal forms of brain cancer - glioblastoma.

Image: Wikipedia.org

Using clever manipulations that exploit both the bacteria’s normal biology and the brain tumor environment, researchers at Duke University created a genetically modified version of Salmonella typhimurium. But how can a strain of bacteria that causes typhoid-like diseases in mice and food poisoning in humans be commandeered to treat brain cancer?

Duke University researchers aimed to extend previous studies that suggest bacterial invasion could potentially kickstart the body’s immune system into fighting tumors. Because attempts using only the detoxified version of S. typhimurium have been unsuccessful, the team knew they would have to add tweaks to outsmart the cancer.

To begin with, the team used a detoxified version of S. typhimurium that was starved for purine - a nucleic acid that just happens to be found in abundance in brain tumors. This has the desired effect of targeting the bacteria to the tumor source.

Then, the team modified the bacteria such that they produced 2 chemicals: Azurin - a pro-apoptotic drug, and p53 - a tumor suppressor protein. These chemicals have the combined effect of inducing cell death. In particular the cellular suicide would occur when oxygen levels are low. Not coincidentally, tumor are well-known to be oxygen-deprived.

The genetic modifications work in concert to stage an unusual attack in glioblastoma tumors. Tested in rat models, the bacteria treatment led to a 19 percent survival rate over 100 days. By contrast, untreated mice survived a median of 26 days.

While nearly 20 percent may not sound impressive, we have to consider that the current median survival time for glioblastoma is around 15 months. "Since glioblastoma is so aggressive and difficult to treat, any change in the median survival rate is a big deal," said Jonathan Lyon, a co-author of the study. "And since few survive a glioblastoma diagnosis indefinitely, a 20 percent effective cure rate is phenomenal and very encouraging."

Of note glioblastoma multiforme is the most common and deadly form of primary brain cancer. In GBM, malignant glial cells form vast networks of tendrils throughout the brain, making it nearly impossible to surgically remove all the cancerous tissues. Dubbed as the “octopus tumor,” GBMs can evade even the most aggressive surgeries, chemotherapies, and radiotherapies, leaving patients with a five-year survival rate of less than 10 percent.

"A major challenge in treating gliomas is that the tumor is dispersed with no clear edge, making them difficult to completely surgically remove. So designing bacteria to actively move and seek out these distributed tumors, and express their anti-tumor proteins only in hypoxic, purine rich tumor regions is exciting," said Ravi Bellamkonda, the study’s senior author. "And because their natural toxicity has been deactivated, they don't cause an immunological response. At the doses we used in the experiments, they were naturally cleared once they'd killed the tumors, effectively destroying their own food source."

The team is conducting further studies to improve the efficacy of this treatment. In particular, they are hopeful that this bacteria-turned-tumor-destroyer platform can be adapted with different drugs to treat multiple tumor types.

Additional source: Duke University

About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
JUL 23, 2018
Cancer
JUL 23, 2018
Increased Vitamin D Is Not Cancer Preventative
A new study in July's JAMA Oncology outlines the results of a 4-year study in New Zealand focused on vitamin D and if it is positively associated with cancer prevention....
JUL 30, 2018
Cancer
JUL 30, 2018
Challenges Coming to a Cancer Diagnosis in the UK
England's NHS Cancer Patient Experience Survey shows some cancers take longer for GPs to recognize....
AUG 07, 2018
Cancer
AUG 07, 2018
Is There a Best Time of Day to Administer Chemo?
A common hematologic cancer chemotherapy agent is looked at for its efficacy on solid tumors and specifically evaluates if delivery time during the day affects is anti-tumor activity....
AUG 30, 2018
Genetics & Genomics
AUG 30, 2018
Genetic Changes can Help Diagnose Childhood Cancers Far Earlier
New research has revealed genetic rearrangements that happen far before bone cancer starts growing in children....
SEP 02, 2018
Cell & Molecular Biology
SEP 02, 2018
Cancer Cell Lines can Evolve in the Lab
New research shows that scientists have to take steps to verify the identity of the cell lines they grow....
SEP 05, 2018
Videos
SEP 05, 2018
Why Glioblastoma Is So Deadly
Senator John McCain passed away recently after battling brain cancer. Most forms of brain cancer are aggressive and difficult to treat because medications...
Loading Comments...