Super suppressor: Boosting a gene that stifles tumor growth

Researchers have packaged a tumor suppressor into a therapeutic nanoparticle.
Researchers have packaged a tumor suppressor into a therapeutic nanoparticle. IMAGE: ISLAM, ET AL.

Most of the time, cancer cells do a combination of two things: they overexpress genes that drive tumor growth and they lose normal genes that typically suppress tumors. No two tumors are exactly alike, but some combination of these two effects is usually what results in cancer. Now, for the first time, researchers have shown that it’s possible to treat cancer by delivering a gene that naturally suppresses tumors.

Researchers from Boston Children’s Hospital, Brigham and Women’s Hospital and Memorial Sloan Kettering Cancer Center combined their cancer biology and nanomaterials expertise and developed a therapeutic capable of delivering a tumor suppressor gene known as PTEN, the loss of which can allow tumors to grow unchecked.

In several preclinical models, their PTENboosting therapeutic was able to inhibit tumor growth. Their findings were published yesterday in Nature Biomedical Engineering.

“In conventional cancer therapies, you are trying to block tumor-fueling genes that cause too much cell growth,” says co-corresponding author Bruce R. Zetter, PhD, a principal investigator in the Boston Children’s Vascular Biology Program. “But that approach doesn’t get at the fact that oftentimes, there has also been a loss of tumor suppressing genes. Now, we’ve provided a proof of concept that it’s possible to inhibit tumor growth by delivering a set of genetic instructions that increase the body’s production of a tumor suppressor — PTEN.

Combining genetics and nanotechnology

To do so, the investigators developed targeted messenger RNA (mRNA) nanoparticles – super-small-scale delivery vehicles that can ferry genetic information into tumor cells.

“Our approach represents the convergence of nanotechnology and biology,” said co-corresponding author Jinjun Shi, PhD, in a press release from Brigham and Women’s. Shi is a faculty member of the Center for Nanomedicine and Associate Professor of Anesthesia at Brigham and Women’s.

Together, the team tested the effects of PTEN mRNA nanoparticles on cultured prostate cancer cells in the lab. They found that the nanoparticles could efficiently infiltrate the cells and restore tumor suppressor function, killing cancer cells. In Zetter’s lab, postdoctoral researcher Yingjie Xu, PhD, helped bring the novel approach to life in cancer models.

In mouse models of metastatic prostate cancer, where the cancer had spread to the bones, Xu and the team saw significant suppression of tumor growth and progression. Using imaging analysis, the team found that the PTEN mRNA delivered via nanoparticles was responsible for the increase in cancer cell destruction. Importantly, they found the therapy to be safe, as the mice showed no significant changes in body weight and no organ toxicity.

“Essentially, we are normalizing tumor cells because we are restoring something that they had before they became cancerous,” said Zetter, who is also the Charles Nowiszewski Professor of Cancer Biology, Surgery at Harvard Medical School.

Parts of this story originally appeared in a Brigham and Women’s press release written by Haley Bridger. 

Learn more about cancer research at Boston Children’s.