Resolving translational challenges in cancer biology through yeast experimental evolution

Area of Science:

• Evolutionary biology
• Cancer biology
• Molecular pathology

Background:

• Cancer genomics, targeted therapy, and immunotherapy have advanced tumor diagnosis and treatment.
• Challenges persist in interpreting variants of uncertain significance, understanding variable penetrance, predicting drug resistance, and identifying early indicators of therapeutic failure.

Purpose of the Study:

• To propose yeast experimental evolution as a practical upstream discovery platform for cancer biology.
• To leverage yeast models for resolving fundamental evolutionary questions in cancer, such as adaptive routes and reproducibility.
• To provide a framework for applying yeast evolution studies to cancer research.

Main Methods:

• Review and organization of representative yeast experimental evolution studies based on evolutionary dynamics.
• Development of design principles and an operational workflow for yeast-based cancer research.
• Analysis of the strengths and limitations of yeast models, including complementary insights from fission yeast.

Main Results:

• Yeast models provide high control, scale, and temporal resolution to expose recurrent adaptive routes, transient intermediates, and compensatory mechanisms.
• These models facilitate the study of genotype-to-fitness relationships that are difficult to resolve in mammalian systems.
• Fission yeast offers unique strengths that complement other model systems.

Conclusions:

• Yeast experimental evolution serves as a valuable upstream discovery platform for cancer biologists.
• This approach can accelerate the understanding of evolutionary dynamics in cancer, informing therapeutic strategies.
• Yeast models help prioritize and refine downstream validation in complex cancer systems.