Abstract
Resistance to drugs is a major problem in cancer chemotherapy. Various cellular mechanisms of drug resistance have been identified in cultured tumor cell lines selected for growth in the presence of sublethal concentrations of various anticancer drugs. They involve drug transport and detoxification, qualitative or quantitative alterations of the drug target, repair of drug-induced DNA lesions, and alterations in signaling or execution of apoptosis. More recently, the possibility to simultaneously analyze the expression of thousands of genes using DNA microarrays has allowed exploring the relationships between gene expression and sensitivity to several anticancer drugs. A number of studies using microarrays for identifying genes governing tumor chemosensitivity focused on tumor cell lines. Some clinical studies have also been carried out to investigate whether tumor gene expression patterns could predict clinical response to chemotherapy. Results of these studies are encouraging, indicating that individualization of drug treatment based on multigenic response-predictive markers is feasible.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Giaccone G. Clinical perspectives on platinum resistance. Drugs 2000; 59(Suppl 4):9–17, (discussion 37-18).
Pluen A, Boucher Y, Ramanujan S et al. Role of tumor-host interactions in interstitial diffusion of macromolecules: Cranial vs. subcutaneous tumors. Proc Natl Acad Sci USA 2001; 98(8):4628–4633.
Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev 2001; 46(1–3):149–168.
Dalton WS. The tumor microenvironment as a determinant of drug response and resistance. Drug Resist Updat 1999; 2(5):285–288.
Broxterman HJ, Lankelma J, Hoekman K. Resistance to cytotoxic and anti-angiogenic anticancer agents: Similarities and differences. Drug Resist Updat 2003; 6(3):111–127.
Dalton WS. The tumor microenvironment: Focus on myeloma. Cancer Treat Rev 2003; 29(Suppl 1):11–19.
Muerkoster S, Wegehenkel K, Arlt A et al. Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma cells involving increased secretion and paracrine effects of nitric oxide and interleukin-lbeta. Cancer Res 2004; 64(4):1331–1337.
Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: Role of ATP-dependent transporters. Nat Rev Cancer 2002; 2(1):48–58.
Tew KD. Glutathione-associated enzymes in anticancer drug resistance. Cancer Res 1994; 54(16):4313–4320.
Poruchynsky MS, Giannakakou P, Ward Y et al. Accompanying protein alterations in malignant cells with a microtubule-polymerizing drug-resistance phenotype and a primary resistance mechanism. Biochem Pharmacol 2001; 62(11):1469–1480.
Gorre ME, Mohammed M, Ellwood K et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293(5531):876–880.
Weisberg E, Griffin JD. Resistance to imatinib (Glivec): Update on clinical mechanisms. Drug Resist Updat 2003; 6(5):231–238.
Sartorius UA, Krammer PH. Upregulation of Bcl-2 is involved in the mediation of chemotherapy resistance in human small cell lung cancer cell lines. Int J Cancer 2002; 97(5):584–592.
Bignami M, Casorelli I, Karran P. Mismatch repair and response to DNA-damaging antitumour therapies. Eur J Cancer 2003; 39(15):2142–2149.
Shah MA, Schwartz GK. Cell cycle-mediated drug resistance: An emerging concept in cancer therapy. Clin Cancer Res 2001; 7(8):2168–2181.
Alaoui-Jamali MA, Dupre I, Qiang H. Prediction of drug sensitivity and drug resistance in cancer by transcriptional and proteomic profiling. Drug Resist Updat 2004; 7(4–5):245–255.
Karp JE. MDR modulation in acute myelogenous leukemia: Is it dead? Leukemia 2001; 15(4):666–667.
Scherf U, Ross DT, Waltham M et al. A gene expression database for the molecular pharmacology of cancer. Nat Genet 2000; 24(3):236–244.
Staunton JE, Slonim DK, Coller HA et al. Chemosensitivity prediction by transcriptional profiling. Proc Natl Acad Sci USA 2001; 98(19):10787–10792.
Musumarra G, Condorelli DF, Scire S et al. Shortcuts in genome-scale cancer pharmacology research from multivariate analysis of the National Cancer Institute gene expression database. Biochem Pharmacol 2001; 62(5):547–553.
Blower PE, Yang C, Fligner MA et al. Pharmacogenomic analysis: Correlating molecular substructure classes with microarray gene expression data. Pharmacogenomics J 2002; 2(4):259–271.
Vekris A, Meynard D, Haaz MC et al. Molecular determinants of the cytotoxicity of platinum compounds: The contribution of in silico research. Cancer Res 2004; 64(1):356–362.
Huang Y, Anderle P, Bussey KJ et al. Membrane transporters and channels: Role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res 2004; 64(12):4294–4301.
Dan S, Tsunoda T, Kitahara O et al. An integrated database of chemosensitivity to 55 anticancer drugs and gene expression profiles of 39 human cancer cell lines. Cancer Res 2002; 62(4):1139–1147.
Zembutsu H, Ohnishi Y, Tsunoda T et al. Genome-wide cDNA microarray screening to correlate gene expression profiles with sensitivity of 85 human cancer xenografts to anticancer drugs. Cancer Res 2002; 62(2):518–527.
Nakatsu N, Yoshida Y, Yamazaki K et al. Chemosensitivity profile of cancer cell lines and identification of genes determining chemosensitivity by an integrated bioinformatical approach using cDNA arrays. Mol Cancer Ther 2005; 4(3):399–412.
Moriyama M, Hoshida Y, Otsuka M et al. Relevance network between chemosensitivity and transcriptome in human hepatoma cells. Mol Cancer Ther 2003; 2(2):199–205.
Mariadason JM, Arango D, Shi Q et al. Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin. Cancer Res 2003; 63(24):8791–8812.
Wallqvist A, Rabow AA, Shoemaker RH et al. Establishing connections between microarray expression data and chemotherapeutic cancer pharmacology. Mol Cancer Ther 2002; 1(5):311–320.
Brown JM. NCI’s anticancer drug screening program may not be selecting for clinically active compounds. Oncol Res 1997; 9(5):213–215.
Kudoh K, Ramanna M, Ravatn R et al. Monitoring the expression profiles of doxorubicin-induced and doxorubicin-resistant cancer cells by cDNA microarray. Cancer Res 2000; 60(15):4161–4166.
Watts GS, Futscher BW, Isett R et al. cDNA microarray analysis of multidrug resistance: Doxorubicin selection produces multiple defects in apoptosis signaling pathways. J Pharmacol Exp Ther 2001; 299(2):434–441.
Zhou Y, Gwadry FG, Reinhold WC et al. Transcriptional regulation of mitotic genes by camptothecin-induced DNA damage: Microarray analysis of dose-and time-dependent effects. Cancer Res 2002; 62(6):1688–1695.
Reinhold WC, Kouros-Mehr H, Kohn KW et al. Apoptotic susceptibility of cancer cells selected for camptothecin resistance: Gene expression profiling, functional analysis, and molecular interaction mapping. Cancer Res 2003; 63(5):1000–1011.
Lamendola DE, Duan Z, Yusuf RZ et al. Molecular description of evolving paclitaxel resistance in the SKOV-3 human ovarian carcinoma cell line. Cancer Res 2003; 63(9):2200–2205.
Kang HC, Kim IJ, Park JH et al. Identification of genes with differential expression in acquired drug-resistant gastric cancer cells using high-density oligonucleotide microarrays. Clin Cancer Res 2004; 10(1 Pt 1):272–284.
Winegarden N. Microarrays in cancer: Moving from hype to clinical reality. Lancet 2003; 362(9394):1428.
Kihara C, Tsunoda T, Tanaka T et al. Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles. Cancer Res 2001; 61(17):6474–6479.
Okutsu J, Tsunoda T, Kaneta Y et al. Prediction of chemosensitivity for patients with acute myeloid leukemia, according to expression levels of 28 genes selected by genome-wide complementary DNA microarray analysis. Mol Cancer Ther 2002; 1(12):1035–1042.
Chang JC, Wooten EC, Tsimelzon A et al. Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet 2003; 362(9381):362–369.
Ayers M, Symmans WF, Stec J et al. Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 2004; 22(12):2284–2293.
Ntzani EE, Ioannidis JP. Predictive ability of DNA microarrays for cancer outcomes and correlates: An empirical assessment. Lancet 2003; 362(9394):1439–1444.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Quintieri, L., Fantin, M., Vizier, C. (2007). Identification of Molecular Determinants of Tumor Sensitivity and Resistance to Anticancer Drugs. In: Mocellin, S. (eds) Microarray Technology and Cancer Gene Profiling. Advances in Experimental Medicine and Biology, vol 593. Springer, New York, NY. https://doi.org/10.1007/978-0-387-39978-2_10
Download citation
DOI: https://doi.org/10.1007/978-0-387-39978-2_10
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-39977-5
Online ISBN: 978-0-387-39978-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)