Evidence map›Paper›PMID 33919753›Full record

ArticleCancers2021

Standing Variations Modeling Captures Inter-Individual Heterogeneity in a Deterministic Model of Prostate Cancer Response to Combination Therapy.

Harsh Vardhan Jain, Inmaculada C Sorribes, Samuel K Handelman, Johnna Barnaby, Trachette L Jackson

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Advances in cancer vaccines for immunotherapy of prostate cancer.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023
    Article
  7. Article
  8. Review
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

5 authors at 4 institutions in 1 country.

Harsh Vardhan JainDepartment of Mathematics & Statistics, University of Minnesota Duluth, Duluth, MN 55812, USA.ORCID 0000-0002-9662-0444
Inmaculada C SorribesDepartment of Mathematics, Duke University, Durham, NC 27708, USA.ORCID 0000-0001-8348-3746
Samuel K HandelmanDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0001-6970-2172
Johnna BarnabyDepartment of Mathematics, Shippensburg University, Shippensburg, PA 17257, USA.ORCID 0000-0001-8396-091X
Trachette L JacksonDepartment of Mathematics, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0003-2803-3341
University of Michigan · USDuke University · USShippensburg University · USUniversity of Minnesota, Duluth · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sipuleucel-T (Provenge) is the first live cell vaccine approved for advanced, hormonally refractive prostate cancer. However, survival benefit is modest and the optimal combination or schedule of sipuleucel-T with androgen depletion remains unknown. We employ a nonlinear dynamical systems approach to modeling the response of hormonally refractive prostate cancer to sipuleucel-T. Our mechanistic model incorporates the immune response to the cancer elicited by vaccination, and the effect of androgen depletion therapy. Because only a fraction of patients benefit from sipuleucel-T treatment, inter-individual heterogeneity is clearly crucial. Therefore, we introduce our novel approach, Standing Variations Modeling, which exploits inestimability of model parameters to capture heterogeneity in a deterministic model. We use data from mouse xenograft experiments to infer distributions on parameters critical to tumor growth and to the resultant immune response. Sampling model parameters from these distributions allows us to represent heterogeneity, both at the level of the tumor cells and the individual (mouse) being treated. Our model simulations explain the limited success of sipuleucel-T observed in practice, and predict an optimal combination regime that maximizes predicted efficacy. This approach will generalize to a range of emerging cancer immunotherapies.

Indexed as

ADTimmunotherapymathematical modelprostate cancerprovengestanding variations

Identifiers

PMID33919753
PMCPMC8070719
OpenAlexW3153356208

What Socratic 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 Socratic graph.