Expression of therapy-induced senescence markers in breast cancer samples upon incomplete response to neoadjuvant chemotherapy
| Autor: | Ahmad T. Mansour, Tareq Saleh, Bilal Azab, Mohammed El-Sadoni, Omar Abuelaish, Valerie J. Carpenter, Mahmoud Al-Balas, Ahmad Alhesa, Heyam Awad |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Senescence Cyclin-Dependent Kinase Inhibitor p21 Aging medicine.medical_treatment Biophysics Cell Death & Injury Breast Neoplasms Biochemistry Methylation Transcriptome 03 medical and health sciences Histone H3 0302 clinical medicine Breast cancer medicine Biomarkers Tumor Humans Lamin B1 Senolytic Molecular Biology Research Articles Cellular Senescence Cancer Chemotherapy Lamin Type B business.industry Neoadjuvant Chemotherapy breast cancers Cell Biology Middle Aged medicine.disease H3K9Me3 Therapeutics & Molecular Medicine Neoadjuvant Therapy Histone Code 030104 developmental biology 030220 oncology & carcinogenesis Cell Cycle Growth & Proliferation Cancer research Female business p21CIP1 Lamin |
| Zdroj: | Bioscience Reports |
| ISSN: | 1573-4935 0144-8463 |
| Popis: | Senescence is a cell stress response induced by replicative, oxidative, oncogenic, and genotoxic stresses. Tumor cells undergo senescence in response to several cancer therapeutics in vitro (Therapy-Induced Senescence, TIS), including agents utilized as neoadjuvant chemotherapy (NAC) in the treatment of invasive breast cancer. TIS has been proposed to contribute to adverse therapy outcomes including relapse. However, there is limited evidence on the induction of senescence in response to NAC in clinical cancer and its contribution to disease outcomes. In this work, the expression of three senescence-associated markers (p21CIP1, H3K9Me3 (histone H3 lysine 9 trimethylation), and Lamin B1) was investigated in breast cancer samples that developed partial or incomplete pathological response to NAC (n=37). Accordingly, 40.54% of all samples showed marker expression consistent with a senescence-like phenotype, while the remainders were either negative or inconclusive for senescence (2.70 and 56.8%, respectively). Moreover, analysis of core-needle biopsies revealed minimal changes in p21CIP1 and H3K9Me3, but significant changes in Lamin B1 expression levels following NAC, highlighting a more predictive role of Lamin B1 in senescence detection. However, our analysis did not establish an association between TIS and cancer relapse as only three patients (8.1%) with a senescence-like profile developed short-term recurrent disease. Our analysis indicates that identification of TIS in tumor samples requires large-scale transcriptomic and protein marker analyses and extended clinical follow-up. Better understanding of in vivo senescence should elucidate its contribution to therapy outcomes and pave the way for the utilization of senolytic approaches as potential adjuvant cancer therapy. |
| Databáze: | OpenAIRE |
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