ArticleScientific reports2016
Differential selective pressure alters rate of drug resistance acquisition in heterogeneous tumor populations.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Optimal control theory as a method for designing multidrug adaptive therapy regimens.NPJ systems biology and applications · 2026Article
- LINC01235 Promotes Clonal Evolution through DNA Replication Licensing-Induced Chromosomal Instability in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Essentiality, protein-protein interactions and evolutionary properties are key predictors for identifying cancer-associated genes using machine learning.Scientific reports · 2024Article
- Strategies to Reduce Long-Term Drug Resistance by Considering Effects of Differential Selective Treatments.Mathematical and computational oncology : third international symposium, ISMCO 2021, virtual event, October 11-13, 2021 : proceedings. ISMCO (Symposium) (3rd : 2021 : Online) · 2021Article
- Impact of chemotherapy on the expression of claudins and cadherins in invasive breast cancer.Experimental and therapeutic medicine · 2019Article
- The influence of tumor heterogeneity on sensitivity of EGFR-mutant lung adenocarcinoma cells to EGFR-TKIs.Translational cancer research · 2019Article
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5 authors.
Funding
Abstract
Recent drug discovery and development efforts have created a large arsenal of targeted and chemotherapeutic drugs for precision medicine. However, drug resistance remains a major challenge as minor pre-existing resistant subpopulations are often found to be enriched at relapse. Current drug design has been heavily focused on initial efficacy, and we do not fully understand the effects of drug selective pressure on long-term drug resistance potential. Using a minimal two-population model, taking into account subpopulation proportions and growth/kill rates, we modeled long-term drug treatment and performed parameter sweeps to analyze the effects of each parameter on therapeutic efficacy. We found that drugs with the same overall initial kill may exert differential selective pressures, affecting long-term therapeutic outcome. We validated our conclusions experimentally using a preclinical model of Burkitt's lymphoma. Furthermore, we highlighted an intrinsic tradeoff between drug-imposed overall selective pressure and rate of adaptation. A principled approach in understanding the effects of distinct drug selective pressures on short-term and long-term tumor response enables better design of therapeutics that ultimately minimize relapse.
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