Molecular tumor profiling: blood test to determine the optimal cancer therapy

If a tumor is diagnosed, tissue samples are usually investigated to determine the molecular tumor profile for personalized cancer treatment. However, tissue biopsy cannot be performed in all affected individuals, e. g. if the tumor tissue is surgically inaccessible or the procedure cannot be performed due to the patient's weak overall condition. Therefore, the University Hospital Zurich has licensed a liquid biopsy for the analysis of more than 300 genes from the company Foundation Medicine/Roche and offers this test as a modern diagnostic method to tumor patients.

In an interview with MEDICA-tradefair.com, Dr. Martin Zoche explains what insights a liquid biopsy can provide in tumor profiling.

How are findings for personalized cancer therapy obtained from liquid biopsy?

Dr. Martin Zoche: In personalized therapy, we look for genomic alterations of tumor DNA, which we have also been able to detect in the blood for several years. To this end, we have established a novel sequencing method in the laboratory and can thus identify the DNA of a solid tumor, for example, a lung or intestinal tumor, in the blood. The technologies for analyzing genomic alterations (NGS, next-generation sequencing) have been known for more than 10 years. What is new, however, is the high sensitivity of NGS and the subsequent bioinformatic evaluation algorithms that now enable the detection of genomic tumor alterations from blood.

How does the subsequent tumor profiling work?

Zoche: We analyze the data we obtain from sequencing using publicly available mutation databases. These mutation databases have been built up worldwide in recent years with research funding and are now a valuable source of information from tumor mutations. This allows us to detect individual pathogenic genomic alterations in a patient's tumor. With this information, the treating oncologist can then make personalized treatment recommendations for the patient.

What are the advantages of the blood test compared to taking a tissue sample?

Zoche: In general, the analysis of a tissue sample is still the gold standard for tumor diagnostics. It allows histological findings to be obtained that are not possible with a blood test. However, tumor DNA from liquid biopsy has the advantage of identifying mutations from different metastases simultaneously. Tissue biopsy typically involves puncturing only one metastasis, which is then used to determine the tumor profile. However, different metastases may have different tumor profiles.

Another advantage is that for those patients for whom we can no longer perform a tissue biopsy at all for health reasons, the blood test offers a very good alternative for tumor profiling. Only a few milliliters of blood are needed for a liquid biopsy. However, we cannot analyze certain changes in DNA, genomic amplifications and fusions, as well from blood as we can from a tissue biopsy.

Where do you still see potential to develop molecular pathology further?

Zoche: Comprehensive molecular tumor profiling is still not performed on all cancer patients. However, this should be part of standard diagnostics today. Low-cost tests also still need to be established in the area of tumor monitoring. Here we are working with diagnostics companies to make such tests available soon to those affected. In the early detection of cancer, there are already approaches, for example by companies in the USA, that test the blood of healthy people for possible tumor DNA. However, a great deal of development work is still needed here, as predicting whether someone has cancer or not is still far from accurate enough. The goal in tumor profiling is to sequence as comprehensively as possible in order to be able to examine the complete tumor genome of those affected. Only in this way can the medical staff treating the cancer discuss and implement all possible personalized therapy options with the affected person.