Evidence map›Paper›PMID 37813486›Full record

ArticleLife science alliance2023

Synergistic effect of antagonists to KRas4B/PDE6 molecular complex in pancreatic cancer.

Paola Briseño-Díaz, Michael Schnoor, Martiniano Bello-Ramirez, Jose Correa-Basurto, Arturo Rojo-Domínguez, Leticia Arregui, Libia Vega, Enrique Núñez-González, Luis Andres Palau-Hernández, Carlos Guadalupe Parra-Torres and 12 more

Open access · goldAbstract read
In one paragraph

Article in Life science alliance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.8field-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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
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

22 authors at 4 institutions in 1 country.

Paola Briseño-DíazDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.ORCID https://orcid.org/0000-0002-4072-2433
Michael SchnoorDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.
Martiniano Bello-RamirezLaboratory of Molecular Modeling and Drug Design of the Higher School of Medicine, National Polytechnic Institute, Mexico City, Mexico.
Jose Correa-BasurtoLaboratory of Molecular Modeling and Drug Design of the Higher School of Medicine, National Polytechnic Institute, Mexico City, Mexico.
Arturo Rojo-DomínguezDepartment of Natural Sciences, Metropolitan Autonomous University, Mexico City, Mexico.ORCID https://orcid.org/0000-0001-5644-4880
Leticia ArreguiDepartment of Natural Sciences, Metropolitan Autonomous University, Mexico City, Mexico.ORCID https://orcid.org/0000-0003-4645-115X
Libia VegaToxicology Department, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), Mexico City, Mexico.ORCID https://orcid.org/0000-0002-4993-5267
Enrique Núñez-GonzálezDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.
Luis Andres Palau-HernándezDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.
Carlos Guadalupe Parra-TorresDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.
Óscar Manuel García CórdovaDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.ORCID https://orcid.org/0000-0002-7240-8844
Ernesto Zepeda-CastillaDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.ORCID https://orcid.org/0000-0001-8481-9934
Eduardo Torices-EscalanteDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.ORCID https://orcid.org/0000-0001-5104-2778
Leticia Domínguez-CamachoDepartment of Surgical Oncology and General Surgery, Hospital 1 de Octubre, ISSSTE, Mexico City, Mexico.
Beatriz Xoconostle-CazaresDepartment of Biotechnology, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.
Marco Antonio Meraz-RíosDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.ORCID https://orcid.org/0000-0001-6748-8117
Sandra Delfín-AzuaraDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.
Dayan Andrea Carrión-EstradaDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.
Nicolas Villegas-SepúlvedaDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.ORCID https://orcid.org/0000-0001-9489-2545
Rosaura Hernández-RivasDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico.
Maria Del Rocio Thompson-BonillaBiomedical and Transnational Research, Genomic Medicine Laboratory, Hospital 1 de Octubre, ISSSTE, México City, Mexico.
Miguel VargasDepartment of Molecular Biomedicine, Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV-IPN), México City, Mexico mavargas@cinvestav.mx.ORCID https://orcid.org/0000-0002-3031-9798
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional · MXInstitute for Social Security and Services for State Workers · MXTecnológico Nacional de México · MXUniversidad Autónoma Metropolitana · MX

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among all human cancers as it is highly resistant to chemotherapy. K-Ras mutations usually trigger the development and progression of PDAC. We hypothesized that compounds stabilizing the KRas4B/PDE6δ complex could serve as PDAC treatments. Using in silico approaches, we identified the small molecules C14 and P8 that reduced K-Ras activation in primary PDAC cells. Importantly, C14 and P8 significantly prevented tumor growth in patient-derived xenotransplants. Combined treatment with C14 and P8 strongly increased cytotoxicity in PDAC cell lines and primary cultures and showed strong synergistic antineoplastic effects in preclinical murine PDAC models that were superior to conventional therapeutics without causing side effects. Mechanistically, C14 and P8 reduced tumor growth by inhibiting AKT and ERK signaling downstream of K-RAS leading to apoptosis, specifically in PDAC cells. Thus, combined treatment with C14 and P8 may be a superior pharmaceutical strategy to improve the outcome of PDAC.

Indexed as

Antineoplastic AgentsCarcinoma, Pancreatic DuctalPancreatic NeoplasmsAnimalsCell Line, TumorHumansMiceAntineoplastic Agents

Identifiers

PMID37813486
PMCPMC10561825
OpenAlexW4387450999

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.