Evidence map›Paper›PMID 32873828›Full record

ArticleScientific reports2020

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer.

Sabina Luszczak, Benjamin S Simpson, Urszula Stopka-Farooqui, Vignesh Krishna Sathyadevan, Lina M Carmona Echeverria, Christopher Kumar, Helena Costa, Aiman Haider, Alex Freeman, Charles Jameson and 9 more

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

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Review
  3. Targeting PI3K/Akt signaling in prostate cancer therapy.Journal of cell communication and signaling · 2023
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 2 countries.

Sabina LuszczakMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Benjamin S SimpsonMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Urszula Stopka-FarooquiMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Vignesh Krishna SathyadevanMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Lina M Carmona EcheverriaMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Christopher KumarMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Helena CostaResearch Department of Pathology, University College London, London, UK.
Aiman HaiderResearch Department of Pathology, University College London, London, UK.
Alex FreemanResearch Department of Pathology, University College London, London, UK.
Charles JamesonResearch Department of Pathology, University College London, London, UK.
Marzena RatynskaResearch Department of Pathology, University College London, London, UK.
Imen Ben-SalhaResearch Department of Pathology, University College London, London, UK.
Ashwin SridharDepartment of Uro-Oncology, UCLH NHS Foundation Trust, London, UK.
Greg ShawDepartment of Uro-Oncology, UCLH NHS Foundation Trust, London, UK.
John D KellyDepartment of Uro-Oncology, UCLH NHS Foundation Trust, London, UK.
Hayley PyeMolecular Diagnostics and Therapeutics Group, University College London, London, UK.
Kathy A GatelyTrinity Translational Medicine Institute, St. James's Hospital Dublin, Dublin 8, Ireland.
Hayley C Whitaker *Molecular Diagnostics and Therapeutics Group, University College London, London, UK.
Susan Heavey *Molecular Diagnostics and Therapeutics Group, University College London, London, UK. s.heavey@ucl.ac.uk.
University College London · GBUniversity College Hospital · GBSt. James's Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

PIM and PI3K/mTOR pathways are often dysregulated in prostate cancer, and may lead to decreased survival, increased metastasis and invasion. The pathways are heavily interconnected and act on a variety of common effectors that can lead to the development of resistance to drug inhibitors. Most current treatments exhibit issues with toxicity and resistance. We investigated the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus a combination of the PIM inhibitor, AZD-1208, and the PI3K/mTOR inhibitor BEZ235 (Dactolisib) to determine their impact on mRNA and phosphoprotein expression, as well as their functional efficacy. We have determined that around 20% of prostate cancer patients overexpress the direct targets of these drugs, and this cohort are more likely to have a high Gleason grade tumour (≥ Gleason 8). A co-targeted inhibition approach offered broader inhibition of genes and phosphoproteins in the PI3K/mTOR pathway, when compared to single kinase inhibition. The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 + BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies.

Indexed as

Antineoplastic AgentsBiphenyl CompoundsCell Line, TumorCell ProliferationCohort StudiesDrug Therapy, CombinationGene Expression Regulation, NeoplasticHumansImidazolesMalePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProstatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1PyridinesAntineoplastic AgentsAZD1208Biphenyl CompoundsdactolisibIBL-302ImidazolesMTOR protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-pim-1proto-oncogene proteins pimPyridinesPyrimidinesQuinolinesRNA, MessengerThiazolidinesThiophenesTOR Serine-Threonine Kinases

Identifiers

PMID32873828
PMCPMC7463239
OpenAlexW3082557629

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.