The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches.
Summary of "The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches."
The ability to prospectively isolate breast cancer cells that initiate tumors when transplanted orthotopically into immunocompromised mice has led to an explosion of work characterizing these cells and establishing ways to target them. Microarray studies screening for novel targets and chemical library screens for effective therapies have implicated signaling pathways, tumor-stromal interactions, miRNAs and possible even piwi-interacting (piRNAs) in the regulation of tumor initiating cell self-renewal. Potential targeting agents including the beta-catenin inhibitor sulforaphane, AKT inhibitor perfosine, hedgehog inhibitor cyclopamine, stromal interaction inhibitor repertaxin, multidrug resistance pump poison dofequifar fumarate, as well as targeted the dual epidermal growth factor family inhibitor lapatinib and many more have all been found to have toxicity against purportedly chemotherapy resistant subpopulations of cancer cells often referred to as tumor initiating cells (TICs). Work using clinical samples is emerging and supports the hypothesis that neoadjuvant chemotherapy can enrich for TICs in residual disease, but strong correlation with long-term outcome is yet to be established. This paper reviews current attempts to targeting TICs and discusses the competing hypotheses to explain breast cancer recurrence and therapy resistance.
Affiliation
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States.
Journal Details
This article was published in the following journal.
Name: Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
ISSN: 1532-2084
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20739212
- DOI: http://dx.doi.org/10.1016/j.drup.2010.08.001
Medical and Biotech [MESH] Definitions
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
Carcinoma, Lobular
A infiltrating (invasive) breast cancer, relatively uncommon, accounting for only 5%-10% of breast tumors in most series. It is often an area of ill-defined thickening in the breast, in contrast to the dominant lump characteristic of ductal carcinoma. It is typically composed of small cells in a linear arrangement with a tendency to grow around ducts and lobules. There is likelihood of axillary nodal involvement with metastasis to meningeal and serosal surfaces. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1205)
Brca1 Protein
The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)
Dermcidins
47-amino acid peptides secreted by ECCRINE GLANDS and having a role in innate cutaneous defense, being antimicrobial to some pathogenic BACTERIA. They are overexpressed by some primary BREAST CANCER cells. They are derived from 110 residue PROTEIN PRECURSORS.
Nimustine
Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.
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