Related Experiment Video
Updated: Jul 17, 2026
08:56
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Oncogene inactivation-induced senescence facilitates tumor relapse
Philipp Schmitt1,2,3, Katrin Hönig1, Maria Teresa Norcia1,4,5,6
1Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Nature Communications
|July 15, 2026
Summary
Targeted cancer therapies can cause relapse by inducing oncogene inactivation-induced senescence (OIIS). This process initially halts tumor growth but creates conditions for recurrence, limiting treatment durability.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Therapy
Background:
- Targeted therapies offer profound tumor regression in oncogene-addicted cancers.
- Long-term efficacy is frequently compromised by acquired resistance and tumor relapse.
Purpose of the Study:
- To investigate the consequences of oncogene inactivation beyond initial tumor regression.
- To define the mechanisms underlying relapse following oncogene-directed therapy.
Main Methods:
- Induction of oncogene inactivation in preclinical cancer models.
- Analysis of cellular senescence and senescence-associated secretory phenotype (SASP).
- In vivo tumor growth, relapse dynamics, and tumor microenvironment characterization using spectral flow cytometry.
Main Results:
- Oncogene inactivation rapidly triggers senescence and a pro-inflammatory SASP.
- Relapse is associated with polyploidy, chromosomal instability, Mdm2 upregulation, and neovascularization.
- Tumor microenvironment shifts towards immunosuppression during relapse.
- OIIS features are observed in human BRAFV600E melanoma treated with vemurafenib.
Conclusions:
- Oncogene inactivation-induced senescence (OIIS) is a critical factor in tumor relapse.
- OIIS creates a pro-tumorigenic microenvironment that favors recurrence.
- Understanding OIIS hallmarks is crucial for developing strategies to improve the durability of targeted cancer therapies.
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