Cancer tumor markers

Serum cancer antigen 125 (CA-125) is the most extensively evaluated tumor marker for ovarian cancer. Unfortunately, the CA-125 determination is non-specific, and elevated levels can be associated with a number of other gynecologic and gastrointestinal diseases. CA-125 levels in a woman without ovarian cancer, though, are static or tend to decrease over time, whereas levels associated with malignancy will continue to rise.10 Since CA-125 is a non-specific marker, there is no standard recommendation for routine screening for prevention of ovarian cancer. 

CA 15-3 serum tumor marker is intended to detect disease recurrence in stage II and stage III breast cancer patients. It has been reported that CA 15-3, together with other suitable markers, is preferred in measuring the effect of applied hormonal therapy or chemotherapy in metastatic disease. Studies have indicated that CA 15-3 assay values are frequently elevated in patients with breast cancer. These... 

Aziz, K. J. Perspectives on tumor marker tests for cancer diagnosis and monitoring. J. Biomed Lab. Sci. 6, 1-9 (1994). 

Hayes, D. F. Serum tumor markers for breast cancer. Proceedings 5th Annual Conference, Adjuvant Therapy in Primary Breast Cancer. In Senn, S. J. (ed) Recent results of cancer research. Heidelberg, Springer-Verlag, pp. 101-113 (1996). 

Hayes, D. F., Bast, R Desch, C. E., et al. A tumor marker utility grading system (TMUGS) A framework to evaluate clinical utility of tumor markers. J. Natl. Cancer Inst. 818, 1456-1466... 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

To date, 16 GST isozymes have been found in humans [48]. Studies of several cancer tissues have revealed the overexpression of different GST isozymes, with GST Pl-1 (GST Pi, GST ji) being the most predominant. For this reason, GST Pl-1 is regarded as a potential tumor marker [5,49-53]. The high expression levels of GST Pl-1 (up to 2.7% of the total cytosolic protein [52]), combined with its detoxification role against xenobiotics, make GST Pl-1 a major player responsible for drug resistance in patients undergoing anticancer chemotherapy [49]. 

The other well-known member of this superfamily is CEA or carcinoem-bryonic antigen. CEA is a widely used tumor marker, especially for monitoring patients with diagnosed colorectal cancer (M5). It is a high-molecular-weight (Afr 200,000, approximately) glycoprotein containing about 60% carbohydrate. In normal colonic cells and in well-differentiated colon carcinomas, the distribution of CEA is apical. However, in undifferentiated colonic tumors, CEA is present on all of the cell membrane (J3). Whether this altered subcellular localization of CEA mediates cancer spread is presently unclear. 

Although TPMT and UGTIAI represent polymorphisms that can be screened in the patient s germline DNA, some cancer pharmacogenetic markers will require screening of the patient s tumor genome. 

Boschman, G. A., Buys, C. H., van der Veen, A. Y Rens, W., Osinga, J., Slater, R. M and Aten, J. A. (1993) Identification of a tumor marker chromosome by flow sorting, DNA amplification in vitro, and in situ hybridization of the amplified product. Genes Chromosom. Cancer 6, 10-16. 

J. L. Carreras, Early diagnosis of recurrent breast cancer with FDG-PET in patients with progressive elevation of serum tumor markers, Q. J. Nucl. Med. 46(2) (2002) 113-121. 

DNA Microarrays for Transcription Profiling Tumor Tissue Microarray and Proteomic Profiling Of Protein Kinases Molecular Profiling for Cancer Therapeutics New Guidelines For Reporting Tumor Marker Studies Conclusions References... 

In the REMARK system, estimated effects (e.g., hazard ratios) with confidence intervals for the marker were recommended for univariant and key multivariable analyses, and a Kaplan-Meier plot was recommended to represent the effect of a tumor marker in a time-to-event outcome. The discussion section should interpret the results in the context of the pre-specified hypothesis and describe limitations of the study as well as implications for future research and clinical value. These guidelines were advocated for reporting of tumor marker studies in breast cancer research and treatment (63). 

MeShane LM, Altman DG, Sauerbrei W et al. Reporting recommendations for tumor MARKer prog-nostie studies (REMARK). Breast Cancer Res TFeat 2006 100 229-235. 

Hayes DF, Ethier S, Lippman ME. New guidelines for reporting of tumor marker studies in breast cancer research and treatment REMARK. Breast Cancer Res Treat 2006 100 237-238. 

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