Abstract
The field of molecular diagnostics is in a state of rapid evolution featuring continuous technology developments and new clinical opportunities for drug selection, predicting efficacy and toxicity, and monitoring disease outcome. The introduction of new anticancer agents targeting the proteasome has created opportunities for the development of companion diagnostics to guide drug use and patient selection. In this chapter the field of molecular diagnostics is reviewed relevant to cancer, and a series of established prognostic factors known to predict the clinical course of multiple myeloma is presented. Biomarkers impacted by the proteasome pathway that may become clinically useful predictors of therapy related outcome are also included. The chapter concludes with a consideration of the emerging field of pharmacogenomics and its potential use for the prediction of drug response for patients treated with proteasome inhibitors.
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References
Keesee SK. Molecular diagnostics: impact upon cancer detection. Expert Rev Mol Diagn 2002;2:91–92.
Poste G. Molecular diagnostics: a powerful new component of the healthcarevalue chain. Expert Rev Mol Diagn 2001;1:1–5.
Leonard DG. The present and future of molecular diagnostics. Mol Diagn 2001;6:71–72.
Vogel CL, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002;20:719–726.
O’Dwyer ME, et al. STI571: an inhibitor of the BCR-ABL tyrosine kinase for the treatment of chronic myelogenous leukaemia. Lancet Oncol 2000;1:207–211.
Amos J, et al. Commercial molecular diagnostics in the U.S.: The Human Genome Project to the clinical laboratory. Hum Mutat 2002;19:324–333.
Ross JS, et al. Integrating diagnostics and therapeutics: revolutionizing drug discovery and patient care. Drug Discov Today 2002;7:859–864.
Morgan GJ, et al. Modern molecular diagnostics and the management of haematological malignancies. Clin Lab Haematol 1998;20:135–141.
Relling MV, et al. Pharmacogenetics and cancer therapy. Nat Rev Cancer 2001;1:99–108.
Taylor JG, et al. Using genetic variation to study human disease. Trends Mol Med 2001;7:507–512.
Diasio RB, et al. The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil. Pharmacology 2000;61:199–203.
Relling MV, et al. Pharmacogenetics and cancer therapy. Nat Rev Cancer 2001;1:99–108.
Pullarkat ST, et al. Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 2001;1:65–70.
Ingelman-Sundberg M. Genetic susceptibility to adverse effects of drugs and environmental toxicants. The role of the CYP family of enzymes. Mutat Res 2001;482:11–19.
Ingelman-Sundberg M. Pharmacogenetics: an opportunity for a safer and more efficient pharmacotherapy. J Intern Med 2001;250:186–200.
Rusnak JM, et al. Pharmacogenomics: a clinician’s primer on emerging technologies for improved patient care. Mayo Clin Proc 2001;76:299–309.
Hess P, et al. Impact of pharmacogenomics on the clinical laboratory. Mol Diagn 1999;4:289–298.
Schena M, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467–470.
Ramaswamy S, et al. DNA microarrays in clinical oncology. J Clin Oncol 2002;20:1932–1941.
Raetz EA, et al. Gene expression profiling. Methods and clinical applications in oncology. Hematol Oncol Clin North Am 2001;15:911–930.
Diasio RB, et al. The role of pharmacogenetics and pharmacogenomics in cancer chemotherapy with 5-fluorouracil. Pharmacology 2000;61:199–203
Los G, et al. Using mRNA expression profiling to determine anticancer drug efficacy. Cytometry 2002;47:66–71.
Slonim DK. Transcriptional profiling in cancer: the path to clinical pharmacogenomics. Pharmacogenomics 2001;2:123–136.
Lightcap ES, et al. Proteasome inhibition measurements: clinical application. Clin Chem 2000;46:673–683.
Adams J. Development of the proteasome inhibitor PS-341. Oncologist 2002;7:9–16.
Elliott PJ, et al. The proteasome: a new target for novel drug therapies. Am J Clin Pathol 2001;116:637–646.
Albanell J, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor LD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 2002;20:110–124.
Hamadeh HK, et al. Discovery in toxicology: mediation by gene expression array technology. J Biochem Mol Toxicol 2001;15:231–242.
Fielden MR, et al. Challenges and limitations of gene expression profiling in mechanistic and predictive toxicology. Toxicol Sci 2001;60:6–10.
Burchiel SW, Knall CM, Davis JW 2nd, Paules RS, Boggs SE, Afshari CA. Analysis of genetic and epigenetic mechanisms of toxicity: potential roles of toxicogenomics and proteomics in toxicology. Toxicol Sci 2001;59:193–195.
Hamadeh HK, et al. An overview of toxicogenomics. Curr Issues Mol Biol 2002;4:45–56.
Ross JS, et al. Techniques in oncology molecular diagnostics. In: Cancer Molecular Diagnostics (Nakamura R, Grody WW, eds). Humana, Totowa, NJ, 2003.
Baldwin AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996;14:649–683.
Rayet B, et al. Aberrant rel/nfkb genes and activity in human cancer. Oncogene 1999;18:6938–6947.
Wang C-Y, et al. Control of inducible chemoresistance: enhanced antitumor therapy through increased apoptosis by inhibition of NF-κB. Nat Med 1999;5:412–417.
Sunwoo JB, et al. Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res 2001 7:1419–1428
Lin ZP, et al. Prevention of brefeldin A-induced resistance to teniposide by the proteasome inhibitor MG-132: involvement of NF-κB activation in drug resistance. Cancer Res 1998;58:3059–3065.
Schenkein D. Proteasome inhibitors in the treatment of B-cell malignancies. Clin Lymphoma 2002;3:49–55.
Adams J. Preclinical and clinical evaluation of proteasome inhibitor PS-341 for the treatment of cancer. Curr Opin Chem Biol 2002;6:493–500.
Mitsiades N, et al. Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications. Blood 2002;99:4079–4086.
Berenson JR, et al. The role of nuclear factor-kappaB in the biology and treatment of multiple myeloma. Semin Oncol 2001;28:626–633.
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Ross, J.S. et al. (2004). Clinical Molecular Diagnostics for Proteasome Inhibitors in Cancer Therapy. In: Adams, J. (eds) Proteasome Inhibitors in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-794-9_21
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DOI: https://doi.org/10.1007/978-1-59259-794-9_21
Publisher Name: Humana Press, Totowa, NJ
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Online ISBN: 978-1-59259-794-9
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