A novel tool has emerged that identifies the evolutionary benefits of multiple myeloma cells against various treatments. The insights it offers can help avert drug resistance in tumors.
Cancer cells are not all alike, even within the same type. While they harbor genetic mutations that transform them into tumor cells, these errors vary from one cell to another. Each cancer comprises various groups of cells exhibiting different mutations, and understanding these groups is essential since one may rise to prominence, leading to treatment resistance. Nonetheless, scientific efforts to explore the characteristics of these cell groups within a tumor have advanced slowly.
A recent study conducted by the H12O-CNIO Haematological Tumours Clinical Research Unit reveals that a method based on evolutionary principles can effectively show how diverse cell populations in multiple myeloma respond to various medications, potentially resulting in drug resistance.
Evolutionary Competition within the Tumor
Cancer can be likened to an ecosystem where slightly different cells compete in an evolutionary struggle, with the most resilient, or those best at resisting treatments, ultimately surviving. The technique utilized by CNIO researcher Larissa Haertle, known as Clonal competition assays, demonstrates in real-time how the different populations of tumor cells adapt to each treatment until a particular group becomes predominant.
This technique is highly visual: different cell populations are stained with various colors, grown together, and exposed to available treatments. Over time, the color of the population that possesses the genetic traits enabling it to withstand the drug used becomes more prevalent in the culture.
A Highly Heterogeneous Tumor
Gaining insight into how distinct cell populations behave is crucial in the case of multiple myeloma, a blood cancer that frequently emerges because of drug resistance. “Multiple myeloma is quite heterogeneous,” Haertle explains. “A single tumor can have numerous genetic alterations, and we must treat it as if it encompasses several different tumors.”
“Clonal competition assays allow us to observe how each cell population within the same myeloma responds to treatments,” she adds. “This method brings us closer to understanding each patient’s heterogeneity than traditional approaches. Additionally, we can observe how the cells evolve in real time.”
More Capable of Surviving and Thriving
Through these experiments, researchers examined the KRAS gene, which is altered in 20% of multiple myeloma patients. They identified that two specific KRAS mutations provide the cells that carry them with a competitive advantage, as these cells proliferated more than their unmutated counterparts during tests.
Furthermore, they found three specific changes in other genes that only benefit tumor cells when exposed to two standard multiple myeloma treatments, giving those cells an adaptive edge.
“When the drugs were applied, all other cells perished, but those with these mutations persisted,” Haertle notes. To prevent the tumor from developing resistance through this mechanism, the authors recommend implementing “breaks” from treatment or altering therapies when these mutations are detected in patients.
The study was carried out by lead author Haertle along with senior author Santiago Barrio at the H12O-CNIO Haematological Tumours Clinical Research Unit, under the direction of JoaquÃn MartÃnez-López, and at the Department of Internal Medicine II of Würzburg Teaching Hospital in Germany.
