Citations to this article
Abstract
The DNA methyltransferase inhibitor decitabine has classically been used to reactivate silenced genes and as a pretreatment for anticancer therapies. In a variation of this idea, this study explores the concept of adding low-dose decitabine (DAC) following administration of chemotherapy to bolster therapeutic efficacy. We find that addition of DAC following treatment with the chemotherapy agent gemcitabine improves survival and slows tumor growth in a mouse model of high-grade sarcoma. Unlike prior studies in epithelial tumor models, DAC did not induce a robust antitumor T cell response in sarcoma. Furthermore, DAC synergizes with gemcitabine independently of the immune system. Mechanistic analyses demonstrate that the combination therapy induces biphasic cell cycle arrest and apoptosis. Therapeutic efficacy was sequence dependent, with gemcitabine priming cells for treatment with DAC through inhibition of ribonucleotide reductase. This study identifies an apparently unique application of DAC to augment the cytotoxic effects of conventional chemotherapy in an immune-independent manner. The concepts explored in this study represent a promising paradigm for cancer treatment by augmenting chemotherapy through addition of DAC to increase tolerability and improve patient response. These findings have widespread implications for the treatment of sarcomas and other aggressive malignancies.
Authors
Wade R. Gutierrez, Amanda Scherer, Jeffrey D. Rytlewski, Emily A. Laverty, Alexa P. Sheehan, Gavin R. McGivney, Qierra R. Brockman, Vickie Knepper-Adrian, Grace A. Roughton, Dawn E. Quelle, David J. Gordon, Varun Monga, Rebecca D. Dodd
Citations to this article in year 2023 (3)
| Title and authors | Publication | Year |
|---|---|---|
|
Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma
Gutierrez WR, Rytlewski JD, Scherer A, Roughton GA, Carnevale NC, Vyas KY, McGivney GR, Brockman QR, Knepper-Adrian V, Dodd RD |
Current issues in molecular biology | 2023 |
|
Inhibitory effect and related mechanism of decitabine combined with gemcitabine on proliferation of NK/T cell lymphoma cells
Lin L, Liu X, Yu H, Deng H, Peng K, Chen J, Zhang C, Jiang T, Liu X |
Frontiers in pharmacology | 2023 |
|
Severity of SARS-CoV-2 infection in children with inborn errors of immunity (primary immunodeficiencies): a systematic review.
Alhumaid S, Al Mutared KM, Al Alawi Z, Sabr Z, Alkhars O, Alabdulqader M, Al Dossary N, ALShakhs FM, Majzoub RA, Alalawi YH, Al Noaim K, Alnaim AA, Al Ghamdi MA, Alahmari AA, Albattat SS, Almubarak YS, Al Abdulmohsen EM, Al Shaikh H, Alobaidan ME, Almusallam HH, Alhassan FM, Alamer MA, Al-Hajji JA, Al-Hajji DA, Alkadi AA, Al Mutair A, Rabaan AA |
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology | 2023 |
