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The CUP Syndrome (cancer of unknown primary) denotes a variation of the disease that does not allow for an easy identification of the primary cancer, but sees metastases in different parts of the body. 3 to 5 out of a hundred patients will receive their cancer diagnosis on the basis of these kinds of metastases. In some CUP cases, doctors – despite intensive diagnostic attempts – cannot determine the primary cancer at all. This leads to a precarious situation for the patient, since the treatment plan is in large parts determined and based on the primary cancer. The idea of oncological precision medicine may offer a way out of this dilemma, since the origin of the primary cancer is less the issue than readily available tumor-biological markers.

Less than 20% of an iceberg is visible above water. The percentage of genes that are relevant to patients with a CUP diagnosis and that can be drawn from conventional procedures such as an immunohistochemistry surely fall even lower than the iceberg’s 20% rate of visibility.

This is where oncological precision medicine comes in. Genes that are relevant to determining the course of action are identified and analyzed. New target-orientated medication is then developed and used in a multitude of clinical trials and individual treatments.

New Methods of Analysis Characterize the Tumor

The PANTHER-test makes an important contribution to personalized tumor treatment as it provides an extensive analysis of gene activity patterns. The 3D spheroid chemosensitivity test moves away from the trial and error principle of conventional cytotoxic treatment. Cytotoxic treatment offers uncertain prospects of success while severely limiting a patient’s quality of life. Thanks to new developments in molecular genetics and bio-medicine, targeted therapies are moving increasingly into the center of medical interest. Targeted therapies focus on a tumor’s individual characteristic mutations or on the increased activity of cancer genes on a molecular level. Innovative procedures such as the PANTHER-test in connection with the MultiOncogen Mutation tests (MOMs), which undertake a comprehensive mutation analysis of the most important cancer and tumor suppression genes, decipher the characteristics of individual cancer genes that offer the key to targeted therapies. Such combinable CancerGenomeLandscape assays are available in different variations according to the problem at hand.

Isolated cell clusters of various sizes from CUP tissue.
Nuclei: blue; tumor-specific markers: green (cytokeratin) and red (EpCAM)
Small cells with violet border: leukocytes.

Optimizing Treatments

Liquid biopsies are a new technique in which a tumor and the treatment tailored to it can be assessed without having to undergo an invasive operation. A mere blood sample is enough. Circulating tumor cells (CTCs) or circulating cell-free tumor DNA (cftDNA) form the basis of liquid biopsies. Using special techniques, CTCs can be isolated and offer insight into a procedure’s success rates. Highly efficient molecular biological techniques allow drawing sufficient RNA and DNA from just one or a few of these CTCs to determine the activity of all of the tumor’s genes via the PANTHER-chip test or MultiOncogen Mutation tests (MOMs). Should it be impossible to extract tumor cells from the blood sample, the MOMs can be used to identify therapeutically relevant mutations from circulating cell-free tumor DNA (cftDNA) in the serum. This test is of particular clinical importance since tumors treated with targeted therapy often change their mutational pattern after six months. If this happens, they no longer respond to the current therapy.

Gentle Cancer Treatment via Personalization

The innovations in developing individual vaccines are bringing the dream of personalized, highly specific and gentle cancer therapy closer to realization. New diagnostic tools, pan-genomic PANTHER gene activity testing and EXOM-MOMs make a significant contribution to the development of individual cancer vaccines.

With regard to the production of such vaccines in particular, it can be of critical importance to cryopreserve part of the tumor tissue after an operation. Uomorphis[LvC1]  offers such cryopreservation, either as standard preservation frozen in the gas phase of liquid nitrogen at a temperature of under -190°C or as LIFE-cryopreservation, in which the tumor cells are isolated and frozen alive in a computer-controlled specialized medium.

To determine the best and most promising course of action in your case, you are very welcome to contact Prof. Bojar for a personal consultation.

We are happy to consult you in finding the right treatment for cup syndrome!

Testing Methods for cup syndrome

CancerGenome Landscape Assay

This most comprehensive molecular-genetic test includes the complete mutational analysis of all human genes that code proteins (exome sequencing) and the activity analysis of the tumor’s entire circa 20.000 genes.

Chemo-/Biopharmaceutical Sensitivity

Using isolated, living tumor cells, this test determines the response to cytotoxic and biopharmaceutical treatments.

MultiOncogen Mutation Tests (MOMs)

MultiOncogen Mutation tests are several, comprehensive mutational tests. When tailored to a specific tumor disease, MOMs identify the mutations relevant to target therapies.


The most comprehensive of the molecular-genetic tests determines the activity of all of a tumor’s genes. It thus allows evaluating the risk of primary breast cancer (OncoAssay Score) and the response to several possible courses of treatment. Suitable for all kinds of tumors.

zirkulierende Tumor DNA

Circulating Tumor DNA

The test identifies mutations in a tumor’s DNA via serum or plasma. It is used within the real-time mutation analysis in several tumor diseases under targeted therapy (real-time liquid biopsy). It allows for a timely discovery of a tumor’s growing resistance to the targeted therapy.

NextGen Oncology Group