ArticleDiscover oncology2025
Aurora Kinase A inhibitor alisertib failed to exert its efficacy on TNBC cells due to consequential enrichment of polyploid giant cancer cells (PGCCs).
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- A peripheral blood-based approach involving vimentin along with AURKA enabled efficient tracking of elusive Oct4/Sox2-expressing disseminated breast cancer stem cells.Bioscience reports · 2026Article
- Overcoming Therapeutic Resistance in Triple-Negative Breast Cancer: Targeting the Undrugged Kinome.International journal of molecular sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
backgroundKinases are emerging as promising targetable choices for Triple negative breast cancer (TNBC) patients who suffer from lack of targeted therapy. Aurora kinase A (AURKA) inhibitor alisertib although showed promise but failed to impart any ultimate benefit in TNBCs. Considering initial preclinical success of alisertib, this study tried to explore the underlying mechanisms of its subsequent insensitivity in TNBCs.
methodsBreast cancer kinome was screened for kinases with high clinical significance by clinical kinase indexing coupled with studying their differential expression pattern and prognostic impact using available datasets. Relevant kinase inhibitors were assessed for pharmacological/toxicological parameters in silico. Alisertib induced polyploid giant cancer cells (PGCCs) were observed microscopically and flow cytometrically. PGCC viability was assessed by single cell MTT and (BrdU) assay. Epithelial and mesenchymal transition (EMT) and stemness markers were examined by immunofluorescence. PGCC enrichment was additionally checked in stained tissue explant/histocultures. Alisertib insensitive cells were developed by repeated alisertib pulsing as confirmed by MTT assay. Alisertib insensitive mammospheres were targeted with mifepristone.
resultsClinical Kinase Index (CKI) scoring and pan cancer expressional profiling coupled with analysis of prognostic effect revealed AURKA as a targetable prognostically relevant kinase. AURKA-targeting agent alisertib demonstrated acceptable pharmacological/toxicological properties but enriched PGCCs in in vitro and tumour histocultures. PGCCs maintained replicative potency producing viable progenies. They retained expression of EMT and stemness markers; demonstrating single cell clonogenicity. PGCC enrichment led to reduced alisertib sensitivity as evident from enrichment of insensitive mammospheres, targetable by mifepristone.
conclusionPGCCs contributed to alisertib insensitivity in TNBCs that may be targeted by mifepristone.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.