Tumor markers: State-of-the-art diagnostics for personalized medicine

When cancer is diagnosed, the terms tumor markers or biomarkers keep popping up. They describe characteristics that are not found in healthy persons. The classic tumor markers can be easily detected in blood samples or other body fluids. Other analysis methods require more effort. Yet they all share one thing in common: biomarkers indicate a potential tumor.


Photo: Hand takes a blood pipe

Tumor markers are measurable substances in the blood that may occur in increased concentrations. They are formed by the cancer cells themselves, or by the body in response to the cancer; © panthermedia.net/ angellodeco

Most of the well-known tumor markers are anything but specific and the evidence of cancer is therefore not always certain. This is why clinical guidelines in Germany do not recommend these markers for cancer diagnosis since a temporary increase in tumor marker levels can also occur in cases of inflammation, pregnancies or in smokers.

Markers with multiple benefits

Tumors possess certain characteristics such as gene mutations for instance or they produce specific proteins that usually do not exist in normal tissue. These distinctive features can be utilized for diagnostic testing since tumor markers can be measured in the patient’s blood or urine for example.

"There are different ways to detect tumors," explains Prof. Wilfried Roth, Assistant Medical Director of the Institute of Pathology at the University of Heidelberg and Director of Molecular Tumor Pathology at the German Cancer Research Center (German: Deutsches Krebsforschungszentrum), DKFZ. "Tumor markers can be detected in the blood in the form of soluble proteins. The prostate-specific antigen (PSA) in prostate cancers is one example of this. However, there are also tissue-based markers or markers that can be detected in other secretions and body fluids like urine or stool."

Photo: histopathologic shot of a kidney

Tissue-based prognostic tumor markers: Immunohistochemical staining of DcR3 protein in kidney carcinoma (brown: DcR3 protein expression; blue: tumor cell nucleus). Tumors with high expression of DcR3 behave more aggressively than DcR3 negative tumors;& copy; Prof. Wilfried Roth

Tumor markers can otherwise be differentiated based on their diagnostic benefits. There are biomarkers that initially indicate whether there actually is a tumor or not. Other markers are used as progression parameters to determine how effective a therapy is. Conversely, if the therapy was successful, the tumor marker can be checked during cancer follow-up care in regular intervals to exclude a disease recurrence. Another benefit is in prognostic or predictive tumor markers that are tissue-based. "A prognostic tumor marker shows how aggressive a tumor is in an individual patient. You measure the specific protein expression in the tumor tissue; the tumor is more aggressive at a higher level of expression. Predictive markers need to be distinguished from them. These are tumor markers that provide information on whether a tumor really responds to the therapy," explains Roth.

However, such markers are not available for all types of cancer and it is actually unclear whether there are markers for all types of cancer: many tumor cells do not differ enough from healthy cells and do not produce markers typical for a cancer type.

A long way to early cancer detection

The idea of using tumor markers as "screening tests" to detect cancers early with a simple blood draw for instance is nothing new. The tumor markers we know so far are still not suited for the early detection of cancer in healthy persons free of symptoms: affected patients are not being diagnosed (lack of sensitivity) while too many healthy persons who are wrongly classified as being sick are needlessly alarmed as well as subjected to redundant exams (lack of specificity).

This is why the strengths of tumor markers still lie in tumor diagnosis, prognosis, therapy surveillance and cancer follow-up care.
Photo: Woman working in the lab in front of an extractor

There are more than 30 different urine biomarker, which are used for the diagnosis of bladder cancer. However, few of these markers are commercially available. The remaining markers are often still in the testing phase;© panthermedia.net/matej kastelic

Tumor marker research is developing at different fronts

Nevertheless, researchers are working on more accurate early detection methods. "One example of this would be the evidence of microRNA molecules in DNA. The keyword here is liquid biopsy. With this technique, cell-free DNA is being detected in the blood. If you subsequently had a tumor-specific mutation at the DNA level, this technique could also be used for early detection. There are different approaches available in this field, but they have so far not been validated sufficiently," explains Roth.

The search for genetic tumor markers provides further potential. In this case, the cancer genome is specifically sequenced and examined. "If you subsequently perform a bioinformatic analysis of this information, you can ultimately design a complete genomic picture of an individual tumor, which in turn provides information on whether the tumor is aggressive, which therapies it could potentially be susceptible to and whether it metastasizes. The vision is to define the tumor as precisely as possible, on the one hand while making the therapy as individual as possible on the other."

Roth sees the diagnostic pathology of tumor markers as one of the largest development fields of biomarker research, namely, with the analysis of biomarkers in living tissue. At the moment, tissue samples are still being destroyed and fixed in formalin. "It would then be possible to specifically test whether certain drugs work. Research should become more active in this area. The tissue reaction to therapy could be examined more closely on the living tissue. Not until then can reliable conclusions on the prognosis and therapy be made."
Photo: Melanie Günther; Copyright: B. Frommann

©B. Frommann

The article was conducted by Melanie Günther and translated from German by Elena O'Meara.