Bacteria-produced molecule shows promise in slowing cancer spread

Researchers from Tulane Cancer Center have identified a naturally occurring molecule produced by bacteria that may help stop cancer from spreading, one of the biggest challenges in cancer treatment.

In a recent study published in Signal Transduction and Targeted Therapy, first author and School of Medicine research scientist Jieqiong Wang, working in the laboratory of Tulane Cancer Center researcher Dr. Hua Lu, discovered that a bacterial signaling molecule called cyclic di-GMP significantly reduced the spread of cancer cells in pre-clinical models, particularly in aggressive breast cancers. The molecule slowed cancer cell movement and dramatically reduced the development of lung metastases while showing very low toxicity.

Metastasis, the spread of cancer from its original site to other organs, is the leading cause of cancer-related deaths. Although many treatments can shrink tumors, preventing cancer from spreading remains a major unmet need.

The study's research team, including Hee-Won Park, research associate professor in the School of Medicine, and Alex Mrozek, researcher in the School of Medicine, found that cyclic di-GMP works by interfering with cellular signals that cancer cells use to migrate and invade other tissues. By blocking key pathways involved in cancer cell movement, the molecule helped limit the ability of tumors to spread.

Importantly, because cyclic di-GMP is produced by bacteria that are naturally existing in the human gut, it's an especially promising candidate for drug development. At the therapeutic dose, it targeted cancer cells through a unique mechanism and showed minimal side effects in animal studies, suggesting it may one day lead to safer therapies designed specifically to prevent cancer spread.

"A broad and practical potential implication of this discovery is that since cyclic di-GMP is a natural product and not toxic to normal cells and tissues as tested at therapeutic doses, it can be readily translated into clinical trials for not only metastatic breast cancers, but also other metastatic cancers, such as melanoma, lung, pancreatic, colorectal, ovarian, prostate and liver cancers," said Lu, the Reynolds and Ryan Families Chair in Translational Cancer Research in the School of Medicine.

While more research is needed before this approach can be tested in patients, the findings point toward a new strategy for treating metastatic cancer. By focusing on preventing tumors from spreading rather than only shrinking existing tumors, scientists hope to develop therapies that improve long-term survival and quality of life for patients.

Lu was recently awarded a one-year, $180,000 Louisiana Board of Regents Support Fund grant to further advance this research.