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Role of the tumor microenvironment in mediating de novo resistance to drugs and physiological mediators of cell death
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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“CAFs comprise the majority of cell types within the TME, and their reciprocal interactions with cancer cells have been well documented (Whiteside, 2008; Hazlehurst et al., 2003; Karnoub et al., 2007).”
From Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism (2016) · cites this paper as Hazlehurst et al., 2003
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Metadata
- Authors
- Hazlehurst, L. A., Landowski, T. H., & Dalton, W. S.
- Affiliations
- University of South Florida (US)
- Corresponding author
- Dalton, William S
- Venue
- Oncogene
- Published
- 2003-10-20
- Volume
- 22
- Issue
- 47
- Pages
- 7396-7402
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- 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
- 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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