Novel Stem Cell Method May Offer an Alternative to Treat Cancer Metastasis

The approach only targets metastatic tissue, reducing negative adverse events associated with chemotherapy.

A novel stem cell-targeting method can effectively attack cancerous tissue while preventing some of the toxic adverse events associated with chemotherapy.

In a study published in Science Translational Medicine, investigators programmed human bone marrow stem cells to identify the unique properties of cancerous tissue. More importantly, they manipulated already engineered cells to detect distinctly stiff cancerous tissue.

Metastatic tumors are responsible for 90% of cancer deaths. Although it has been a focal point of cancer research, little progress has been made to improve treatment for metastasis, according to the study authors.

For the study, scientists sought to leverage the central role of the mechanoenvironment in cancer metastasis. The developed the mechanoresponsive cell system (MRCS), which is designed to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo.

The engineered stem cells were transplanted into mouse models of metastatic breast cancer that had spread to the lung. Once the stem cells settled into the tumor site, they secreted cytosine deaminase enzymes.

Next, the mice were administered an inactive chemotherapy called 5-flurocytosine, which was triggered by the cytosine deaminase enzymes.

“This is a new paradigm for cancer therapy,” said investigator Weian Zhao. “We are going in a direction that few have explored before, and we hope to offer an alternative and potentially more effective cancer treatment.”

The authors believe that this stem cell-based approach could serve as an alternative to different chemotherapies.

“Our new type of treatment only targets metastatic tissue, which enables us to avoid some of conventional chemotherapy’s unwanted side effects,” Zhao said. “This published work is focused on breast cancer metastases in the lungs. However, the technology will be applicable to other metastases as well, because many solid tumors have the hallmark of being stiffer than normal tissue. This is why our system is innovative and powerful, as we don’t have to spend the time to identify and develop a new generic or protein marker for every kind of cancer.”

Thus far, the method’s safety and efficacy have been demonstrated in preclinical animal studies. The investigators hope to transition to human clinical trials soon.

Currently, the investigators are expanding their research to include other types of cells, including CAR-T cells, to treat metastatic breast and colon cancers. They also plan to adjust the technology for use in other diseases, such as diabetes and fibrosis.