Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr;91(4):345-360.
doi: 10.1007/s00280-023-04523-w. Epub 2023 Mar 24.

A three-marker signature identifies senescence in human breast cancer exposed to neoadjuvant chemotherapy

Mohammed El-Sadoni #  1 , Sofian Al Shboul #  2 , Ahmad Alhesa  1 , Nisreen Abu Shahin  1 , Elham Alsharaiah  3 , Mohammad A Ismail  4 , Nidaa A Ababneh  4 , Moureq R Alotaibi  5 , Bilal Azab  1   6 , Tareq Saleh  7
Affiliations

A three-marker signature identifies senescence in human breast cancer exposed to neoadjuvant chemotherapy

Mohammed El-Sadoni et al. Cancer Chemother Pharmacol. 2023 Apr.

Abstract

Purpose: Despite the beneficial effects of chemotherapy, therapy-induced senescence (TIS) manifests itself as an undesirable byproduct. Preclinical evidence suggests that tumor cells undergoing TIS can re-emerge as more aggressive divergents and contribute to recurrence, and thus, senolytics were proposed as adjuvant treatment to eliminate senescent tumor cells. However, the identification of TIS in clinical samples is essential for the optimal use of senolytics in cancer therapy. In this study, we aimed to detect and quantify TIS using matched breast cancer samples collected pre- and post-exposure to neoadjuvant chemotherapy (NAC).

Methods: Detection of TIS was based on the change in gene and protein expression levels of three senescence-associated markers (downregulation of Lamin B1 and Ki-67 and upregulation of p16INK4a).

Results: Our analysis revealed that 23 of 72 (31%) of tumors had a shift in the protein expression of the three markers after exposure to NAC suggestive of TIS. Gene expression sets of two independent NAC-treated breast cancer samples showed consistent changes in the expression levels of LMNB1, MKI67 and CDKN2A.

Conclusions: Collectively, our study shows a more individualized approach to measure TIS hallmarks in matched breast cancer samples and provides an estimation of the extent of TIS in breast cancer clinically. Results from this work should be complemented with more comprehensive identification approaches of TIS in clinical samples in order to adopt a more careful implementation of senolytics in cancer treatment.

Keywords: Breast cancer; Ki-67; Lamin B1; Neoadjuvant chemotherapy; Senescence; p16INK4a.

PubMed Disclaimer

References

    1. Saleh T, Bloukh S, Carpenter VJ, Alwohoush E, Bakeer J, Darwish S, Azab B, Gewirtz DA (2020) Therapy-induced senescence: an “old” friend becomes the enemy. Cancers (Basel) 12:822. https://doi.org/10.3390/cancers12040822 - DOI - PubMed
    1. Wang B, Kohli J, Demaria M (2020) Senescent cells in cancer therapy: friends or foes? Trends Cancer 6:838–857. https://doi.org/10.1016/j.trecan.2020.05.004 - DOI - PubMed
    1. Beck J, Horikawa I, Harris C (2020) Cellular senescence: mechanisms, morphology, and mouse models. Vet Pathol 57:747–757. https://doi.org/10.1177/0300985820943841 - DOI - PubMed
    1. Wang X, Tsao S-W, Wong Y-C, Cheung A (2003) Induction of senescent-like growth arrest as a new target in anticancer treatment. Curr Cancer Drug Targets 3:153–159. https://doi.org/10.2174/1568009033482001 - DOI - PubMed
    1. Robles SJ, Adami GR (1998) Agents that cause DNA double strand breaks lead to P16INK4a enrichment and the premature senescence of normal fibrolasts. Oncogene 16:1113–1123. https://doi.org/10.1038/sj.onc.1201862 - DOI - PubMed

Publication types

Substances

LinkOut - more resources