Evidence map›Paper›PMID 41764979›Full record

ReviewTranslational oncology2026

The Hippo pathway in clear cell renal cell carcinoma (ccRCC): a nexus with the VHL disruption?

T Waeckel, R Lefranc, M Waeckel, M Riffet, X Tillou, G Levallet, C Bazille

Abstract readReview
In one paragraph

Review in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. 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

7 authors.

T WaeckelUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Urologie et Transplantation, 14000 CAEN, France. Electronic address: waeckel-t@chu-caen.fr.
R LefrancUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Urologie et Transplantation, 14000 CAEN, France.
M WaeckelUniversité Technologique de Compiègne, France.
M RiffetUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Anatomopathologie, 14000 CAEN, France.
X TillouUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Urologie et Transplantation, 14000 CAEN, France.
G LevalletUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Anatomopathologie, 14000 CAEN, France.
C BazilleUniversité de Caen Normandie, CNRS, Normandie Univ, ISTCT UMR6030, CYCERON, F-14000 Caen, France; Centre Hospitalier Universitaire de Caen Normandie, Service d'Anatomopathologie, 14000 CAEN, France.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClear cell renal cell carcinoma (ccRCC) represents 70% of kidney cancers, with 20-50% recurrence risk after surgery. Despite therapeutic advances, no reliable biomarkers have been identified for patient stratification or treatment response prediction. While VHL gene alterations are well-established in ccRCC pathogenesis, the role of the Hippo pathway remains underexplored despite ample evidence of its involvement.

objectiveThis review synthesizes current knowledge on Hippo pathway alterations in ccRCC and examines its crosstalk with the VHL/HIF axis, identifying potential biomarkers and therapeutic targets. STRATEGY: We comprehensively analyzed literature on Hippo pathway components in ccRCC, focusing on molecular mechanisms, clinical correlations, and interactions with VHL signaling.

resultsMultiple Hippo pathway alterations characterize ccRCC: RASSF1A hypermethylation, NF2 mutations (particularly in aggressive variants), SAV1 downregulation associated with 14q loss, and LATS1/2 methylation-mediated inactivation. These changes result in YAP/TAZ nuclear accumulation and oncogenic transcription. Importantly, chromosome 3p loss simultaneously disrupts both VHL and RASSF1, creating a unique double-hit scenario. The VHL-Hippo crosstalk operates through multiple mechanisms: HIF-induced GPRC5A and VEGFR signaling inhibit LATS1/2 phosphorylation, promoting YAP/TAZ activation, while active YAP/TAZ enhances pro-angiogenic gene transcription, amplifying hypoxic responses. Low expression of RASSF1A, SAV1, and LATS1/2, coupled with high YAP/TAZ activity, correlates with advanced tumor stage, higher grade, and poorer survival.

conclusionsThe Hippo pathway represents a critical yet underappreciated dimension of ccRCC biology, offering promising biomarkers for risk stratification and novel therapeutic targets. The Hippo-VHL nexus presents multiple intervention points that could enhance current treatment.

Indexed as

BiomarkerClear cell renal cell carcinomaEmerging therapeutic strategyHippo pathwayVHL

Identifiers

PMID41764979
PMCPMC12966756

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.