- CA72-4
- Gastrointestinal cancer
- tumor marker
- ovarian cancer
- pancreatic cancer
In the management of metastatic and recurrent cancer, it is vital to assess response to antitumor therapy. The most commonly used methodology is by serial measurement of tumor size on physical examination or imaging studies employing the response evaluation criteria in solid tumors (RECIST) criteria. As an adjunct to direct measurement of lesions, several tumor markers including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and cancer antigen 125 (CA125) have obtained United States Food and Drug Administration (FDA) approval for the monitoring of various gastrointestinal and gynecologic malignancies. These tumor markers along with cancer antigen 27-29 (CA27-29) used in the monitoring of breast cancer are proteins shed by cancer cells and are readily measured in the laboratory using antibodies.
The utility of serial measurement of CA19-9, CEA, and CA125 in predicting treatment response in pancreatic, colon and ovarian cancer has been validated in multiple studies (1-4). Frequent serial measurements can easily be obtained and have the potential of alerting the clinician to the need for timely assessment of a patient for treatment failure, allowing for earlier intervention. In addition, tumor markers may at times have greater accuracy in assessing response since imaging studies using RECIST criteria are not totally reliable as they do not always differentiate viable tumor from residual fibrosis or scarring. Nevertheless, their usefulness in tumor monitoring has been limited by their inconsistent and variable elevation in various malignancies, the need for a relatively large tumor burden to cause an elevation, frequent false-positive elevations in non-malignant conditions, and by lack of conviction by the oncological community to accept an increase or decrease in the tumor marker as a surrogate for disease progression or response. Thus, there remains and unmet need for development of new biomarkers for assessment of tumor burden and response to therapy. While rapidly-evolving research utilizing analysis of circulating tumor DNA as well as proteomics is underway, we continue to rely on traditional techniques such as measuring of concentrations of abnormal proteins shed by various cancer types.
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In addition to the conventional tumor markers CEA, CA27-29, CA19-9 and CA125 there is another tumor marker, tumor-associated glycoprotein 72 (TAG-72) developed years ago used world-wide which never gained US FDA approval. This is a 48-kDa mucin-like glycoprotein complex, identified with the monoclonal antibody B72.3, a murine antibody raised against a membrane-enriched fraction from a human breast carcinoma liver metastasis (5). CA72-4 antigen is an antigenic determinant of the TAG-72 glycoprotein, which is also recognized by the B72.3 and CC-49 monoclonal antibodies (6). This antigen has been found in a variety of human adenocarcinomas including colorectal, gastric, ovarian, breast, and lung, however, it is rarely expressed in benign and normal adult tissues (7-9).
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While CA125, CEA and CA19-9 currently are standard tumor markers for ovarian, gastrointestinal (i.e. stomach, colon and small bowel) and pancreatic cancer, respectively, CA72-4 remains a potentially superior biomarker for these types of cancer.
The DRG TM CA72.4 enzyme-linked immunosorbent (ELISA) kit is a solid-phase sandwich assay, utilizing CC-49 antibody, developed by DRG International (New Jersey, USA) and validated as a standalone assay to be employed in the individual hospital and laboratory setting. Using the DRG TM CA72-4 ELISA assay, the current study aimed to i) quantify the rate of elevation of the tumor marker CA72-4 in each cancer type compared to the rate of elevation of other current FDA-approved tumor biomarkers, and ii) correlate levels of CA72-4 to clinical outcomes in patients with measurable disease.
- Received May 1, 2017.
- Revision received May 16, 2017.
- Accepted May 19, 2017.
- Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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