Tumor markers colon cancer

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. 

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. 

Microsatellite instability (MSI) in the tumor caused by defeetive DNA mismateh repair has been associated with outeome to ehemotherapy (34). For example, a study of 320 Dukes B2 and C colon cancers treated with 5-FU therapy showed that MSI status was eorrelated with improved survival (p = O.OI) (35). MSI is also associated with a mutator phenotype that may lead to mutations in pharmaeogenetic markers, which would not be pieked up by screening the germline genome. 

New antigenic compounds from colon tumor tissue have been isolated and antibodies have been produced. These antigens are not detectable in extracts of normal colon tissue. The antigens may be suitable as markers of colon cancer. 

Elevated levels of CKl have been demonstrated in prostate cancer and small cell carcinoma of the lung. Although it is also elevated in other malignancies, such as those of the breast, colon, ovary, and stomach, the clinical usefulness of CKl as a tumor marker requires further investigation. CK isoenzymes have been included in a prostate cancer panel, ProstAsure. ... 

CEA is a marker for colorectal, gastrointestinal, lung, and breast carcinoma. CEA was discovered by Gold and Freeman in 1965. Rabbits were immunized with extracts of human colon cancer tissue, and the resultant antisera were absorbed with extracts of normal human colon. Some antisera reacted with the tumor extracts but not with the extracts... 

FIGURE 2.15 Detection of microsatellite instability using the NCI recommended panel of five microsatellite markers. In this colon cancer sample, all five markers show microsatellite instability, which manifests as change in size of microsatellite repeats seen on capillary gel electropherograms of tumor PCR products. Electropherograms of normal tissue PCR products are used as a negative control. 

An example of the application of the microchip-based immunosorbent assay is shown below. The human carcinoembryonic antigen (CEA), one of the most widely used tumor markers for serodi-agnosis of colon cancer, was assayed with a microchip-based system [9]. An ultratrace amount of CEA dissolved in serum samples was successfully determined within a short time. Polystyrene beads pre-coated with anti-CEA antibody were introduced into a microchannel. Then a serum sample containing CEA, the first antibody, and the second antibody conjugated with colloidal gold. 

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