Drs. Bogdan Czerniak (left) and Marek Kimmel (right) discuss their collaborative research related to the bladder cancer program project grant that was recently funded by the National Institutes of Health (NIH).
A recent study by researchers at Rice University and the University of Texas MD Anderson Cancer Center is drawing broad attention for shedding light on how bladder cancer develops and for its potential to transform the diagnostic and treatment landscape of this cancer.
The work, featured on the cover of the Journal of Pathology—where it was published in September—and highlighted in Nature Reviews Urology, provided researchers with foundational evidence that led to a recent grant from the National Institute of Health worth over $10 million. This grant award will allow a team of researchers from various U.S. research institutions and universities including MD Anderson, Rice, Columbia, and Rochester to conduct a more comprehensive study on the development of early bladder cancer using biological, mathematical and AI-based modeling approaches.
Bogdan Czerniak of MD Anderson and Rice's Marek Kimmel co-led the initial study and used mathematical modeling to reconstruct the long, hidden timeline of urothelial carcinoma, a frequent and invasive cancer of the bladder and urinary tract. By analyzing the full set of mutations present across the organ, the researchers estimated how long it takes for the disease to emerge and how it evolves from early, unnoticed changes to aggressive tumor growth.
Kimmel and his Rice team adapted a mathematical model they introduced in 2022—based on a type of Markov branching process—to track how mutations accumulate and spread. In simple terms, the model simulates how individual mutations “branch” over time, how new ones appear, and how some die out, allowing the researchers to work backward from the final pattern of mutations to the cancer’s starting point.
Using this approach, the study found that bladder cancer typically develops over approximately 30 years. For most of that time, the cancer remains in a dormant phase in which early mutations grow slowly and quietly. The disease then enters a fast-moving progressive phase, lasting fewer than five years, marked by a rapid surge in harmful mutations and the expansion of cancerous cells.
The model also revealed that different groups of mutations dominate at different times. Alpha (α) mutations appear earliest and persist for decades, beta (β) mutations surge during the shift from dormancy to progression, and gamma (γ) mutations arise only in the last two years—driving swift tumor growth leading up to diagnosis.
“Our model has demonstrated that the development of bladder cancer is a multi-decade process involving two major stages with specific sets of mutations dominating each stage,” Kimmel said. “It provides unique insights into how bladder cancer evolves, facilitating the identification of novel targets for early detection, treatment, and prevention.”
The initial study’s dual recognition by leading journals in the field and its ability to attract a major federal grant award underscores its importance in understanding ithe incipient events that lead to urothelial carcinogenesis. By illuminating when key events occur, the newly funded project is expected to guide future strategies for early detection of bladder cancer and in developing interventions to prevent these tumors from becoming invasive.