GRAND RAPIDS, Mich. (WOOD) — Scientists at Van Andel Institute have started to unravel the mystery surrounding treatment-resistant cancers. Their findings, published today in Molecular Cell, shed light on the molecular mechanisms that cause a specific gene mutation, STK11, to initiate an inflammatory cascade. What they uncovered were hidden inflammatory triggers that can damage healthy cells and make common chemotherapy and immunotherapies more challenging for success.

Dr. Russell Jones, the chair of VAI’s Department of Metabolism and Nutritional Programming, emphasized that understanding the connection between the mutation and cancer development is a crucial step toward devising improved treatments.

“Our study identifies important features of these cancers and suggests that targeting inflammation may make these tumors more responsive to treatment,” Jones said.

STK11 mutations occur when disruptions in the gene’s instructions lead to insufficient production of the protein LKB1. LKB1 is a tumor suppressor that regulates cell growth. Without adequate LKB1 levels, the normal checks and balances within cells are compromised, allowing cancerous cells to increase unchecked. These mutations are particularly common in treatment-resistant lung cancer, pancreatic cancer, cervical cancer, and Peutz-Jehgers Syndrome, a rare condition associated with an increased risk of digestive tract cancer development.

Before today’s research was published, scientists had recognized a link between LKB1 and cancer, but they were not sure about the mechanism that allowed tumors to grow. They now have a better understanding that when the body loses LKB1, it triggers an epigenetic change in cells. Since LKB1 regulates the body’s defense mechanisms, inflammation, against injury and infection, the lack of the protein allows for uncontrolled inflammation which then damages healthy cells and pushes them closer to malignancy.

“It’s a perfect storm of problems for which we now have potential solutions,” said Shelby Compton, a Van Andel Institute Graduate School Ph.D. student and the study’s first author. “In addition to cancer, I hope this work will inform new therapeutic strategies for Peutz-Jehgers Syndrome, which has few treatments and no cure.”

With the study now published, the next step Jones says is to “put ideas into action”. The research team is committed to developing targeted strategies aimed at combating inflammation in LKB1-associated cancers.