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- Title
Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy.
- Authors
Tai, Isabella T.; Dai, Meiru; Owen, David A.; Chen, Lan Bo
- Abstract
Overcoming resistance to chemotherapy and radiation therapy has been a difficult but important goal in the effort to cure cancer. We used gene-expression microarrays to identify differentially expressed genes involved in colorectal cancer resistance to chemotherapy and identified secreted protein, acidic and rich in cysteine (osteonectin) (SPARC) as a putative resistance-reversal gene by demonstrating low SPARC expression in refractory human MIP101 colon cancer cells. We were able to achieve restoration of their radiosensitivity and sensitivity to 5-fluorouracil and irinotecan by reexpression of SPARC in tumor xenografts. Moreover, treatment of mice with SPARC conferred increased sensitivity to chemotherapy and led to significant regression of xenografted tumors. The results show that modulation of SPARC expression affects colorectal cancer sensitivity to radiation and chemotherapy. SPARC-based gene or protein therapy may ameliorate the emergence of resistant clones and eradicate existing refractory clones and offers a novel approach to treating cancer.
- Subjects
CANCER treatment; THERAPEUTICS; PHARMACOLOGY; CELLULAR pathology; FLUOROPYRIMIDINES; CELLS; ANIMAL experimentation; ANTINEOPLASTIC agents; CAMPTOTHECIN; CELL lines; COLON tumors; COMPARATIVE studies; DRUG resistance in cancer cells; FLUOROURACIL; GENES; GLYCOPROTEINS; RESEARCH methodology; MEDICAL cooperation; MICE; RESEARCH; TUMORS; XENOGRAFTS; EVALUATION research; OLIGONUCLEOTIDE arrays; GENE expression profiling
- Publication
Journal of Clinical Investigation, 2005, Vol 115, Issue 6, p1492
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI23002