Evidence map›Paper›PMID 35158939›Full record

ArticleCancers2022

Dual Inhibition of Myc Transcription and PI3K Activity Effectively Targets Colorectal Cancer Stem Cells.

Miriam Gaggianesi, Laura Rosa Mangiapane, Chiara Modica, Vincenzo Davide Pantina, Gaetana Porcelli, Simone Di Franco, Melania Lo Iacono, Caterina D'Accardo, Francesco Verona, Irene Pillitteri and 9 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. 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

19 authors at 2 institutions in 1 country.

Miriam GaggianesiDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-7810-856X
Laura Rosa MangiapaneDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0003-4186-0157
Chiara ModicaDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.
Vincenzo Davide PantinaDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0003-1144-0434
Gaetana PorcelliDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.
Simone Di FrancoDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-6217-2161
Melania Lo IaconoDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-9292-327X
Caterina D'AccardoDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.
Francesco VeronaDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0001-6226-4624
Irene PillitteriDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.
Alice TurdoDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-6152-4903
Veronica VeschiDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-6379-7366
Ornella Roberta BrancatoDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-2783-0720
Giampaolo MuratoreDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-5447-3992
Giuseppe PistoneDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.
Maria Rita BongiornoDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0002-6355-2588
Matilde TodaroDepartment of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.ORCID 0000-0001-8686-8043
Ruggero De MariaDipartimento di Medicina e Chirurgia Traslazionale, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
Giorgio StassiDepartment of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy.
University of Palermo · ITUniversità Cattolica del Sacro Cuore · IT

Funding

Italian Association for Cancer Research AIRC IG 16746Italian Association for Cancer Research AIRC IG 21492Ministero della Salute RF2018-12367044Ministero dell'Università e della Ricerca 2017WNKSLR
6 · The paper itself

Abstract

Despite advances in the curative approach, the survival rate of advanced colorectal cancer (CRC) patients is still poor, which is likely due to the emergence of cancer cell clones resistant to the available therapeutic options. We have already shown that CD44v6-positive CRC stem cells (CR-CSCs) are refractory toward standard anti-tumor therapeutic agents due to the activation of the PI3K pathway together with high HER2 expression levels. Tumor microenvironmental cytokines confer resistance to CR-CSCs against HER2/PI3K targeting by enhancing activation of the MAPK pathway. Here, we show that the CSC compartment, spared by BRAF inhibitor-based targeted therapy, is associated with increased expression levels of CD44v6 and Myc and retains boosted clonogenic activity along with residual tumorigenic potential. Inhibition of Myc transcription, downstream of the MAPK cascade components, and PI3K pathway activity was able to overcome the protective effects of microenvironmental cytokines, affecting the survival and the clonogenic activity of CR-CSCs, regardless of their mutational background. Likewise, the double targeting induced stabilization of mouse tumor avatars. Altogether, these data outline the rationale for dual kinase targeting of CR-CSCs to prevent their adaptive response, which would lead to disease progression.

Indexed as

anti-tumor drug resistancecancer stem cellscolorectal cancercombination therapies

Identifiers

PMID35158939
PMCPMC8833549
OpenAlexW4213225746

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.