Researchers on the University of Michigan Rogel Cancer Center and School of Dentistry found that certain drugs can change the elemental makeup of cancer stem cells in mouse models of mucoepidermoid carcinoma – a lethal type of salivary gland cancer that currently has no treatment options. These results appeared in Clinical Cancer Research.

We observed that once we used small molecule inhibitors of MDM2 for a brief time period, the population of cancer stem cells decreased quite a bit.”

Jacques Nor, D.D.S, M.S,. Ph.D., Donald Kerr Professor of Dentistry and Study’s Lead Creator

The team initially thought that the cancer stem cells were being selectively killed by this drug, however the study revealed something more profound. Cancer stem cells represent the small variety of cells in a tumor that fuel cancer’s growth and spread.

“We found that the drug actually changes the elemental nature of the cells to make them more vulnerable to other therapies and fewer capable of start recent tumors.”

Nor’s team also observed that the incidence of relapse in mice treated with this drug was much lower than within the mice that weren’t treated.

Mucoepidermoid carcinoma is probably the most common malignant salivary gland cancer with very limited therapeutic options. Over 3,000 people die of the disease in america every 12 months, and to this point there isn’t a FDA approved drug to treat it.

“There’s currently no effective therapy for this cancer. At once, these patients are typically treated with radical surgery and radiation, and that sometimes is insufficient. Patients die due to tumor relapse and tumor metastasis. We’d like a systemic drug. That is one among the primary outcomes that’s showing some positive signs when it comes to tumor regression or inhibiting tumor relapse,” Nor said.

Nor has been studying for years drugs that activate P53 to see if this makes cancer cells more vulnerable to therapies. In 2019, he and his team published a study in Clinical Cancer Research that showed that small molecule inhibitors work well in mouse-models of MEC, however the team still hadn’t determine just how the drugs work. This recent study moves the team one step closer to that understanding.

P53 is often mutated in most cancers but rarely in MEC, which made these small molecule inhibitors a very good candidate to check. “This drug requires a non-mutated type of P53 to work,” said Nor. “In mucoepidermoid carcinoma, this drug works well because P53 shouldn’t be mutated.” These results show that P53 is integral to MEC and suggest that therapeutic activation of p53 could present recent treatment options for patients, possibilities that energize Nor and his team.

“The underside line is we now have a drug that’s in a clinical trial for patients with salivary gland cancer,” he said.

Source:

Journal reference:

Rodriguez-Ramirez, C., et al. (2022) p53 Inhibits Bmi-1-driven Self-Renewal and Defines Salivary Gland Cancer Stemness. Clinical Cancer Research. doi.org/10.1158/1078-0432.CCR-22-1357.