# SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16 positive cancer cells

**Authors:** Ryan Wallis, Bethany K. Hughes, Madeleine Moore, Emily A. O’Sullivan, Luke C. McIlvenna, Luke Gammon, Anthony Hope, Fiona Bellany, Parul Dixit, Claire Mackenzie, Charlotte Green, David Gray, Cleo L. Bishop

PMC · DOI: 10.18632/aging.206333 · Aging (Albany NY) · 2025-10-30

## TL;DR

Researchers developed SAMP-Score, a machine learning tool to identify compounds that induce senescence in certain cancer cells, potentially offering new treatment options.

## Contribution

The novel contribution is the development of SAMP-Score, a morphology-based machine learning method for identifying pro-senescence compounds in p16 positive cancers.

## Key findings

- SAMP-Score identifies senescence induction in senescence marker positive cancers using morphological profiles.
- QM5928 is a novel pro-senescence compound that induces senescence in various Sen-Mark+ cancers.

## Abstract

Background: Senescence identification is rendered challenging due to a lack of universally available biomarkers. This represents a bottleneck in efforts to develop pro-senescence therapeutics – agents designed to induce the arrest of cellular proliferation associated with a senescence response in cancer cells for therapeutic gain. This is particularly true in contexts such as basal-like breast cancer (BLBC), which often express high levels of widely reported senescence hallmarks, which has led to the designation of these subtypes as senescence marker positive (Sen-Mark+). Unfortunately, these are often cancers with the most limited treatment options, where novel pro-senescence compounds would be of potential clinical utility.

Results: To address these challenges, we have developed SAMP-Score, a machine learning classification tool for identifying senescence induction in Sen-Mark+ cancers. This technique builds upon our previous observation that senescent cells develop distinct senescence-associated morphological profiles (SAMPs), which can be assessed readily in traditionally challenging contexts for senescence identification, including high-throughput screens.

Conclusions: Through application of SAMP-Score, we have identified QM5928, a novel pro-senescence compound, that is able to induce senescence in a variety of Sen-Mark+ cancers and has potential utility as a tool molecule to explore the mechanisms and pathways through which senescence induction occurs in these cells.

## Linked entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029]
- **Diseases:** basal-like breast cancer (MONDO:0004984), cancer (MONDO:0004992)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}
- **Diseases:** BLBC (MESH:D001943), cancer (MESH:D009369)
- **Chemicals:** QM5928 (-)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12822720/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12822720/full.md

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Source: https://tomesphere.com/paper/PMC12822720