Show-Me State Times

A team of scientists at the University of Missouri has made a significant discovery that could address a major challenge in lung cancer treatment. The researchers, led by Dhananjay Suresh, Anandhi Upendran, and Raghuraman Kannan from Mizzou’s School of Medicine, have identified a molecular interaction between two proteins, AXL and FN14, within cancer cells. This interaction may explain why some patients initially respond to drug treatments but experience resistance after 18 months.

Initially focusing on blocking the AXL protein, Suresh developed a treatment in 2019 that proved ineffective as tumors continued to grow. To counter this issue, the research team has now created a gelatin-based nanoparticle capable of targeting both proteins simultaneously. Early studies using mice have shown promising results with tumors responding positively to this dual-target treatment.

“If we can stop both sides of the seesaw from moving, we may finally be able to keep these drugs working,” said Kannan. “Our study shows that the tumor is successfully responding to the treatment, so these results will provide us with a solid foundation for further investigations.”

Lung cancer remains the leading cause of cancer-related deaths in the United States according to the American Cancer Society. Kannan's work focuses on advancing research for patients whose tumors carry specific gene mutations responsive to tyrosine kinase inhibitors. However, these tumors often develop resistance over time.

“The tumor becomes smart, evolving mechanisms to resist treatment and continue growing despite continued drug therapy,” explained Kannan.

Although not yet ready for clinical application, this dual-target therapy represents progress in understanding and combating drug resistance. Future research will investigate whether similar molecular interactions occur with other proteins.

“This helps fill in a huge black hole in our understanding of drug resistance,” said Kannan. “It gives us a new path forward — and fresh hope that lung cancer can become a manageable, chronic disease instead of a life-threatening one.”

The study titled “Nanoparticle-mediated cosilencing of drug resistance and compensatory genes enhances lung cancer therapy” was published in ACS Nano with contributions from Soumavo Mukherjee, Ajit Zambre, Shreya Ghoshdastidar, Sairam Yadavilli, Karamkolly Rekha alongside Upendran at Mizzou.