| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Molecular Oncology, Markers, Clinical Correlates |
Section of Medicine and Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom; University of Southern California, Los Angeles, California; and Royal Marsden National Health Service Trust, Sutton, Surrey SM2 5N9, United Kingdom
Purpose: The purpose of this research was to evaluate the predictive value of expression of thymidylate synthase (TS) and other genes for response to raltitrexed (RTX).
Experimental Design: Twenty-five patients with metastatic colorectal cancer received RTX 3 mg/m2 3-weekly. Pretreatment tumor biopsies were analyzed for TS, dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), folylpolyglutamate synthetase, and reduced folate carrier mRNA expression by real-time reverse transcription-PCR. TS protein expression was evaluated by immunohistochemistry using a polyclonal TS antibody.
Results: Twenty patients were evaluable for response and gene expression. Six of 20 (30%) achieved a partial response. Median TS/ß-actin was 5.7 x 103 (range, 2.2–42 x 103). Median TS/ß-actin was 3.7 x 103 in responding patients and 6.1 x 103 in nonresponders (P = 0.048). Five of 6 patients with TS/ß-actin 
4.1 x 103 and 1 of 14 with higher values responded (P = 0.002). Overall survival was 21.7 months in patients with TS/ß-actin 4.1 x 103 and 5.7 months in patients with higher values (P = 0.013). No correlations were seen between expression of TP, DPD, reduced folate carrier, or folylpolyglutamate synthetase mRNA and response or survival. Weak TS staining was seen in 10 of 21 tumors evaluable for immunohistochemistry, including 5 responders All 4 of the patients with both weak staining and TS/ß-actin 4.1 x 103 responded.
Conclusions: High TS mRNA expression predicts nonresponse to RTX. By contrast with 5-fluorouracil, high levels of TP and DPD mRNA are not associated with RTX resistance. Limited genomic fingerprinting could optimize single-agent therapy, allowing combinations to be reserved for high TS-expressing patients or for treatment failures, with potential reductions in toxicity and cost.
This article has been cited by other articles:
|
|
 |
|
  L. R. Moreira, A. Almeida Schenka, P. Latuff Filho, H. Nascimento, C. S. Passos Lima, M. A. Silva Trevisan, and J. Vassallo Correlation Between Thymidylate Synthase Protein Expression and Gene Polymorphism with Clinicopathological Parameters in Colorectal Carcinoma International Journal of Surgical Pathology, June 1, 2009; 17(3): 181 - 186. [Abstract] [PDF]
|
|
|
|
 |
|
 B. Sanchez-Espiridion, A. Sanchez-Aguilera, C. Montalban, C. Martin, R. Martinez, J. Gonzalez-Carrero, C. Poderos, C. Bellas, M. F. Fresno, C. Morante, et al. A TaqMan Low-Density Array to Predict Outcome in Advanced Hodgkin's Lymphoma Using Paraffin-Embedded Samples Clin. Cancer Res., February 15, 2009; 15(4): 1367 - 1375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Pandyra, R. Berg, M. Vincent, and J. Koropatnick Combination Silencer RNA (siRNA) Targeting Bcl-2 Antagonizes siRNA against Thymidylate Synthase in Human Tumor Cell Lines J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 123 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sanchez-Aguilera, C. Montalban, P. de la Cueva, L. Sanchez-Verde, M. M. Morente, M. Garcia-Cosio, J. Garcia-Larana, C. Bellas, M. Provencio, V. Romagosa, et al. Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma Blood, July 15, 2006; 108(2): 662 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Napieralski, K. Ott, M. Kremer, K. Specht, H. Vogelsang, K. Becker, M. Muller, F. Lordick, U. Fink, J. Rudiger Siewert, et al. Combined GADD45A and Thymidine Phosphorylase Expression Levels Predict Response and Survival of Neoadjuvant-Treated Gastric Cancer Patients Clin. Cancer Res., April 15, 2005; 11(8): 3025 - 3031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Lecomte, J.-M. Ferraz, F. Zinzindohoue, M.-A. Loriot, D.-A. Tregouet, B. Landi, A. Berger, P.-H. Cugnenc, R. Jian, P. Beaune, et al. Thymidylate Synthase Gene Polymorphism Predicts Toxicity in Colorectal Cancer Patients Receiving 5-Fluorouracil-based Chemotherapy Clin. Cancer Res., September 1, 2004; 10(17): 5880 - 5888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Popat, A. Matakidou, and R. S. Houlston Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Systematic Review and Meta-Analysis J. Clin. Oncol., February 1, 2004; 22(3): 529 - 536. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
