Evidence map›Paper›PMID 32695118›Full record

ArticleFrontiers in immunology2020

Delicate Balances in Cancer Chemotherapy: Modeling Immune Recruitment and Emergence of Systemic Drug Resistance.

Anh Phong Tran, M Ali Al-Radhawi, Irina Kareva, Junjie Wu, David J Waxman, Eduardo D Sontag

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 35 citations in OpenAlex.

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  17. How Should Cancer Models Be Constructed?Cancer control : journal of the Moffitt Cancer Center
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 5 institutions in 2 countries.

Anh Phong TranDepartment of Chemical Engineering, Northeastern University, Boston, MA, United States.
M Ali Al-RadhawiDepartment of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States.
Irina KarevaMathematical and Computational Sciences Center, School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, United States.
Junjie WuClinical Research Institute, Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
David J WaxmanDepartment of Biology and Bioinformatics Program, Boston University, Boston, MA, United States.
Eduardo D SontagDepartment of Electrical and Computer Engineering, Northeastern University, Boston, MA, United States.
Northeastern University · USArizona State University · USBoston University · USCenter for Systems Biology · USZhejiang Provincial People's Hospital · CN

Funding

HEPATIC METABOLISM OF ANTICANCER DRUGSR01CA049248 · NCI · DANA-FARBER CANCER INSTITUTE · PI WAXMAN, DAVID J · 1991 to 2014
$4.3M
NCI NIH HHS R01 CA049248
6 · The paper itself

Abstract

Metronomic chemotherapy can drastically enhance immunogenic tumor cell death. However, the mechanisms responsible are still incompletely understood. Here, we develop a mathematical model to elucidate the underlying complex interactions between tumor growth, immune system activation, and therapy-mediated immunogenic cell death. Our model is conceptually simple, yet it provides a surprisingly excellent fit to empirical data obtained from a GL261 SCID mouse glioma model treated with cyclophosphamide on a metronomic schedule. The model includes terms representing immune recruitment as well as the emergence of drug resistance during prolonged metronomic treatments. Strikingly, a single fixed set of parameters, adjusted neither for individuals nor for drug schedule, recapitulates experimental data across various drug regimens remarkably well, including treatments administered at intervals ranging from 6 to 12 days. Additionally, the model predicts peak immune activation times, rediscovering experimental data that had not been used in parameter fitting or in model construction. Notably, the validated model suggests that immunostimulatory and immunosuppressive intermediates are responsible for the observed phenomena of resistance and immune cell recruitment, and thus for variation of responses with respect to different schedules of drug administration.

Indexed as

Models, TheoreticalAdministration, MetronomicAnimalsAntineoplastic AgentsBrain NeoplasmsCell Line, TumorCyclophosphamideDrug Resistance, NeoplasmGliomaHumansMiceMice, SCIDXenograft Model Antitumor AssaysAntineoplastic AgentsCyclophosphamidecancer resistancecyclophosphamideimmune recruitmentmathematical modelingmetronomic chemotherapy

Identifiers

PMID32695118
PMCPMC7338613
OpenAlexW2996606983

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.