The future role of tumour markers in disease management

Since 1997 there has been major funding by the National Cancer Institute (NCI) in the USA on research for new diagnostic, prognostic and predictive cancer markers. Funding is also provided for translating research techniques that have been used on cell lines or animal models into clinical use, to assist oncologists when selecting the correct treatment strategies.

Completion of the first stage of the Human Genome Project has provided sequence data and has advanced to the next stage of confirming the gene sequence, as well as identifying the expressed products of these genes (Collins et al., 1998).

The NCI has established the Cancer Genome Anatomy Project (CGAP), which is developing a catalogue of genes associated with cancer. This resource for reading the molecular signatures/portraits of cancer from mRNA-extracted material of archived paraffin-embedded tissue is compared with normal tissue using analysis of gene chips to find those with increased or decreased expression of specific mRNAs (Strausberg et al., 1997, 2000). To date, over 1000 000 gene expressed sequence tags (EST) have been deposited in this public bioinformatics cDNA library database, together with their histological reports, TNM (tumour, node, metastasis), staging and clinical outcome data (Lal et al., 1999; Strausberg, 2001; Strausberg et al., 2003).

Work is now under way to identify proteins associated with the expressed mRNA using proteomics. Outcomes of this research are expected over the next 10 years. One of the main aims is to identify suitable early detection cancer tumour markers and other markers for predicting prognosis. The results of ongoing clinical studies, using existing tumour markers, may provide information on which are the best to use (NCI, 2001).

The next few years will see a further development in assay technology, 'protein chips'. These chips will include miniaturized versions of existing tumour assays, allowing multiplex testing on small sample volumes using high-throughput systems, contributing to a tumour profiling approach for patients with cancer.

Other approaches are being investigated to examine circulating autoantibodies which are raised against the tumour markers themselves. In patients with cancer, these would be expected to be higher than in cancer-'free' individuals. In the case of MUC-1, serial serum samples from primary breast cancer patients showed significant correlation between tissue staining and circulating autoantibodies.

As a result of the heterogeneous nature of cancers the use of multiple biomarkers can increase the sensitivity of tumour markers (Cheung et al., 2002).

The appropriate use of tumour markers will greatly assist the clinical management of an individual's cancer in the future. Such 'tests' will aid the monitoring of a patient and potentially alert the clinician at an earlier stage to a possible recurrence, thereby influencing survival.

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