Evidence map›Paper›PMID 41961223›Full record

ArticleBreast cancer (Tokyo, Japan)2026

Targeting breast cancer senescence in 3D models of bone metastasis.

Eleane C B Hamburger, Mansoureh Mohseni Garakani, Saber Ghazizadeh, Saleh Alfaisali, Jean A Ouellet, Michael H Weber, Livia Garzia, Lisbet Haglund, Derek H Rosenzweig

Abstract read
PubMed Publisher
In one paragraph

Article in Breast cancer (Tokyo, Japan), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
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

9 authors.

Eleane C B HamburgerDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Mansoureh Mohseni GarakaniDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Saber GhazizadehDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Saleh AlfaisaliDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Jean A OuelletDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Michael H WeberDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Livia GarziaDepartment of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Lisbet Haglund *Department of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada.
Derek H Rosenzweig *Department of Surgery, Montreal General Hospital , McGill University , Room C10.148.2, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada. derek.rosenzweig@mcgill.ca.ORCID http://orcid.org/0000-0002-6593-8177

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemotherapeutic treatment of breast cancer with Doxorubicin can induce tumor and stromal cell senescence leading to therapy-resistance. Senescence-associated secretory phenotype (SASP) promotes secretion of pro-inflammatory and tumorigenic factors causing systemic inflammation. Combined, this can result in immune suppression, tumor growth and secondary spread of cancer. Targeting and removing senescent and cancerous cells using a combination of chemotherapeutic and senolytic drugs may reduce systemic inflammation, improve therapeutic efficacy, and prevent metastasis. Treatment of triple negative breast cancer (MDA-MB-231) cells and primary spine osteoblasts with 0.25 µM Doxorubicin showed significant induction of senescence indicated by p21 positive cells. Doxorubicin and senolytics (RG-7112, o-Vanillin) treatment of mono-culture MDA-MB-231, MCF7 and MDA-MB-453 breast cancer subtype spheroids indicated efficacy against growth and metabolic activity. Co-culture of triple negative spheroids with treat showed a significant additive effect on decreased tumor sphere viability and growth in a bone-like microenvironment. This was correlated with decreased p21 and Ki-67 proliferation marker in both the breast cancer and osteoblast cells. In all cases, combined Doxorubicin and senolytics significantly reduced sphere size and cancer cell outgrowth, indicating reduced metastatic potential. SASP analysis in the conditioned media from treated co-cultures indicated significant reduction in IL-6 protein secretion and trends in reduction of INFγ, TNFα and IL-1β. Our preclinical data suggests that adding senolytic drugs to chemotherapy could potentially improve clearance of tumors and help regenerate surrounding stroma tissue such as in the bone metastatic environment.

Indexed as

Bone NeoplasmsBreast NeoplasmsCellular SenescenceDoxorubicinSenotherapeuticsTriple Negative Breast NeoplasmsCell ProliferationCoculture TechniquesFemaleHumansMCF-7 CellsMDA-MB-231 CellsOsteoblastsSenescence-Associated Secretory PhenotypeSpheroids, CellularTumor MicroenvironmentDoxorubicinSenotherapeuticsSpine metastases; therapy induced senescence; breast cancer; senolytics; tumor microenvironment; 3D culture

Identifiers

PMID41961223

What OpenQuestion holds

Textmetadata
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.