For 40 percent of women with triple negative breast cancer, the most aggressive type of breast cancer, the cancer will come back and spread – even after the tumor is resected and treated with chemotherapy or radiation.

A cancer research startup company founded by Virginia Tech scientists at the Fralin Biomedical Research Institute at VTC recently received a boost in funding through the U.S. Small Business Administration to study a molecule that could prevent breast cancer recurrence and metastasis.

The company, Acomhal Research Inc., recently secured a one-year $400,000 Small Business Technology Transfer (STTR) grant to determine if a molecule that prevents invasive brain cancer stem cells from spreading can also help treat aggressive forms of breast cancer.

“We’ve shown that this drug has promising therapeutic properties in treating aggressive brain cancers, but we want to know if it can prevent other invasive cancers from spreading, starting with triple negative breast cancer,” said Samy Lamouille, an assistant professor at the Fralin Biomedical Research Institute and chief executive officer of Acomhal Research Inc.

Patients with triple negative breast cancer are more likely to develop new tumors, or metastases, in other organs, such as the brain or lung. Lamouille explains that these recurrences can be spurred by lingering cancer stem cells.

“Cancer stem cells are usually resistant to chemotherapy. If even a small population of these cells are left behind after treatment, then they can rapidly seed the growth of new tumors,” Lamouille said.

Cancer stem cells can also become highly invasive, by tapping into the same cellular signaling programs that are essential during development and help differentiate cells. When this process, called epithelial-mesenchymal transition, is reactivated during cancer progression it can contribute to the metastasis.

By targeting invasive cancer cells, Acomhal’s approach is based on hypothesis that the peptide drug may improve survival rates for women with aggressive forms of breast cancer.

In the pilot study that led to this STTR award, Acomhal demonstrated that the drug works by targeting a set of proteins that help a cancer cell invade new territory. These proteins, secreted by cancer cells during epithelial-mesenchymal transition, degrade the web of macromolecules that surround cells and help keep them in place. This, in turn, carves out a path for invasive cells to break off from the tumor, seep into the blood stream, and colonize new tissue elsewhere.

When Acomhal’s research team added the peptide to metastatic breast cancer cells in a lab dish, the drug decreased levels of the proteins that enable the cancer’s invasive characteristics.

Triple negative breast cancer cells targeted by peptide drug
The peptide drug, tagged in red, targets fast-growing triple negative breast cancer cells and helps curb cell proliferation by blocking a key protein interaction required for cell growth and movement. Cell membranes are shown in green and nuclei are blue. (Acomhal Research, Inc.).

“By targeting these proteins that are really important for invasion, we may be able to inhibit metastasis,” said Lamouille, who is also an assistant professor in the College of Science’s Department of Biological Sciences, and at the Virginia Tech Carilion School of Medicine.

The drug works by competing with a protein, called connexin 43, for key binding sites on microtubules within the cancer cell. Every human cell – including cancerous ones – have microtubules that help the cells move around, expand, and eventually divide. These hollow protein pipes also serve as microscopic highways for protein transport within the cell.

Five years ago, Lamouille found that when connexin 43 cannot bind to microtubules, it reduces the cancer cell’s invasive qualities and curbs proliferation. This discovery led Lamouille and co-founder Robert Gourdie to establish Acomhal, allowing them to continue studying the drug’s cancer-fighting properties and, one day, bring it to market.

Gourdie is a professor and director of the Center for Heart and Reparative Medicine Research at the Fralin Biomedical Research Institute. He is also among the five inventors who developed the peptide that Acomhal studies, which is patented through the Medical University of South Carolina.

This isn’t the biotech startup’s first STTR award, and Lamouille is hopeful that it won’t be the last.

In 2017, the company was awarded $224,999 in STTR funding to develop biodegradable nanoparticles that slowly release the drug to treat mice with human-derived glioblastoma tumors – a highly aggressive, chemo-resistant type of brain cancer. The nanoparticles significantly decreased the number of cancer stem cells within the tumor, reduced cancer cell invasion at tumor borders, and increased survival rates.

These studies showed that the peptide not only stalls cancer stem cell growth, but could also reduce the odds of tumor regrowth in aggressive brain cancers.

“We got all of the results we hoped for with our first Phase I STTR for brain cancer, and we are applying for a Phase II grant to help us lay the foundation for clinical trials in humans,” Lamouille said.

If the company can secure additional funding and all goes as planned, Lamouille says that Acomhal will pursue clinical trials in brain cancer patients within the next few years.

“Ultimately our goal is to help cancer patients. This funding will help us conduct the studies we need to one day pursue clinical trials in humans and, hopefully, improve lives,” Lamouille said.