Cited by 203Cancer Cells and MetastasisCell death mechanisms and regulationAcute Myeloid Leukemia Research

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Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death

Hazlehurst, Lori A, Landowski, Terry H, Dalton, William S·2003·Oncogene

DOI 10.1038/sj.onc.1206943

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Abstract

The emergence of clinical drug resistance continues to be an obstacle for the successful treatment of cancer. Our current understanding of mechanisms associated with drug resistance has been ascertained by investigating drug-resistant models created by exposing a parental population to increasing concentrations of a cytotoxic. These unicellular drug-resistant models have been critical in elucidating drug-resistant mechanism and in some cases have aided in the identification of drug targets. However, these models do not address resistance mechanisms that contribute to de novo drug resistance. We propose that specific niches within the tumor microenvironment may provide a sanctuary for subpopulations of tumors cells that affords a survival advantage following initial drug exposure and may facilitate the acquisition of acquired drug resistance. More specifically, we propose that the bone marrow microenvironment is a sanctuary for hema-topoietic cancers. This review will focus on the bone marrow microenvironment and its role in conferring resistance to cytotoxics and physiological mediators of cell death.

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Authors: Hazlehurst, L. A., Landowski, T. H., & Dalton, W. S.
Affiliations: University of South Florida (US)
Corresponding author: Dalton, William S
ORCID: Hazlehurst, Lori A
Dalton, William S
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2003-10-20
Volume: 22
Issue: 47
Pages: 7396-7402
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1206943
OpenAlex: W2041997066
Cited by: 203
References: 61
Citations by year: 2026: 2 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 19 · 2019: 2 · 2018: 3 · 2017: 9 · 2016: 14 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 18
FWCI: 1.02
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords: tumor microenvironment, acquired drug resistance, bone marrow microenvironment, hematopoietic tumors, cytotoxic drugs, cell death, cancer stem cells, hematopoietic stem cells
MeSH terms: Animals, Antineoplastic Agents, Cell Adhesion, DNA Damage, Humans, Neoplasms, Signal Transduction, Integrins, Apoptosis, Drug Resistance, Neoplasm

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Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death

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