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Scheduled Seminars on Sept. 30, 2025

Speaker
Erez Persi
PI/Lab
Eugene Koonin
Time
11 a.m.
Presentation Title
How Cancers Remain Fit ? From population genetics to cancer therapy
Location
Hybrid
In-person: Building 38A/B2N14 NCBI Library or Meeting Link

Contact NLMDIRSeminarScheduling@mail.nih.gov with questions about this seminar.

Abstract:

Cancer evolution is marked by genome instability, involving aberrations of all scales, from point mutations to whole genome duplications, under constantly changing environmental conditions. How these distinct aberrations co-evolve to maintain cancers fitted throughout tumor progression, remains incompletely understood. Using population genetics to analyze cancer patients’ data, I will provide evidence that aberrations accumulate in a temporal order. This order is determined by a balance between the genomic burden imposed by each aberration and the selective pressures acting on the tumor genome. We identify compensatory relationships among aberrations, manifested by their contrasting clinical outcomes, leading to robust tumor fitness over time. This compensatory relationship appears to be universal as it holds also in species evolution. Further, I will discuss how therapy affects the evolutionary trajectories of tumors, with resistance tumors shifting towards neutral evolution and concomitant worse prognosis. Finally, I will discuss how metabolic and epigenetic adaptations (phenotypic plasticity) to harsh environmental conditions in the tumor microenvironment are linked to mutagenesis, and how the complex relationship between phenotypic plasticity and genome evolution can expose cancer to vulnerabilities that may be exploited for therapeutics and assist clinical decision-making.

References:
1. Persi et al. Criticality in tumor evolution and clinical outcomes. PNAS (2018).
2. Persi et al. Systems analysis of intracellular pH vulnerabilities for cancer therapy. Nat Com (2018).
3. Persi et al. Repeat instability in cancer and adjacent normal tissues. PNAS (2019).
4. Persi et al. Mutation-Selection balance and compensatory mechanisms in tumor evolution. Nat Rev Gen (2021).
5. Persi et al. Compensatory relationship between LCR and gene paralogy in the evolution of prokaryotes. PNAS (2023)
6. Persi et al. Genome-level selection as a universal marker of resistance to therapy. Nat Com (2025).

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