ArticleCancer research2012
Evolutionary approaches to prolong progression-free survival in breast cancer.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 159 citations in OpenAlex.
- Article
- Ensemble Optimal Control for Managing Drug Resistance in Cancer Therapies.Bulletin of mathematical biology · 2026Article
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- A Systematic Review of Evidence for the Cost of Therapeutic Resistance in Cancer.bioRxiv : the preprint server for biology · 2025Article
- Review
- Review
- Adaptive Therapy Exploits Fitness Deficits in Chemotherapy-Resistant Ovarian Cancer to Achieve Long-Term Tumor Control.Cancer research · 2025Article
- Systems biology successes and areas for opportunity in prostate cancer.Endocrine-related cancer · 2025Review
- Medical digital twins: enabling precision medicine and medical artificial intelligence.The Lancet. Digital health · 2025Review
- Bringing evolutionary cancer therapy to the clinic: a systems approach.NPJ systems biology and applications · 2025Review
- Validation of polymorphic Gompertzian model of cancer through in vitro and in vivo data.PloS one · 2025Article
- Article
- Multicellular model of neuroblastoma proposes unconventional therapy based on multiple roles of p53.PLoS computational biology · 2024Article
- Contrasting Dynamics of Intracellular and Extracellular Antibiotic Resistance Genes in Response to Nutrient Variations in Aquatic Environments.Antibiotics (Basel, Switzerland) · 2024Article
- A war on many fronts: cross disciplinary approaches for novel cancer treatment strategies.Frontiers in genetics · 2024Review
- Drug dependence in cancer is exploitable by optimally constructed treatment holidays.Nature ecology & evolution · 2024Article
- Intermetastatic and Intrametastatic Heterogeneity Shapes Adaptive Therapy Cycling Dynamics.Cancer research · 2023Article
- The acquisition order of leukemic drug resistance mutations is directed by the selective fitness associated with each resistance mechanism.Scientific reports · 2023Article
- Mathematical Model of Clonal Evolution Proposes a Personalised Multi-Modal Therapy for High-Risk Neuroblastoma.Cancers · 2023Article
- A survey of open questions in adaptive therapy: Bridging mathematics and clinical translation.eLife · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Many cancers adapt to chemotherapeutic agents by upregulating membrane efflux pumps that export drugs from the cytoplasm, but this response comes at an energetic cost. In breast cancer patients, expression of these pumps is low in tumors before therapy but increases after treatment. While the evolution of therapeutic resistance is virtually inevitable, proliferation of resistant clones is not, suggesting strategies of adaptive therapy. Chemoresistant cells must consume excess resources to maintain resistance mechanisms, so adaptive therapy strategies explicitly aim to maintain a stable population of therapy-sensitive cells to suppress growth of resistant phenotypes through intratumoral competition. We used computational models parameterized by in vitro experiments to illustrate the efficacy of such approaches. Here, we show that low doses of verapamil and 2-deoxyglucose, to accentuate the cost of resistance and to decrease energy production, respectively, could suppress the proliferation of drug-resistant clones in vivo. Compared with standard high-dose-density treatment, the novel treatment we developed achieved a 2-fold to 10-fold increase in time to progression in tumor models. Our findings challenge the existing flawed paradigm of maximum dose treatment, a strategy that inevitably produces drug resistance that can be avoided by the adaptive therapy strategies we describe.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.