Abstract
Epitope detection in monocytes (EDIM) represents a liquid biopsy exploiting the innate immune system. Activated monocytes (macrophages) phagocytose unwanted cells/cell fragments from the whole body including solid tissues. As they return to the blood, macrophages can be used for a non-invasive detection of biomarkers, thereby providing high sensitivity and specificity, because the intracellular presence of biomarkers is due to an innate immune response. Flow cytometry analysis of blood enables the detection of macrophages and phagocytosed intracellular biomarkers. In order to establish a pan-cancer test, biomarkers for two fundamental biophysical mechanisms have been exploited. The DNaseX/Apo10 protein epitope is a characteristic of tumor cells with abnormal apoptosis and proliferation. Transketolase-like 1 (TKTL1) is a marker for an anaerobic glucose metabolism (Warburg effect), which is concomitant with invasive growth/metastasis and resistant to radical and apoptosis inducing therapies. The detection of Apo10 and TKTL1 in blood macrophages allowed a sensitive (95.8%) and specific (97.3%) detection of prostate, breast and oral squamous cell carcinomas. Since TKTL1 represents a drugable target, the EDIM based detection of TKTL1 enables a targeted cancer therapy using the vitamin derivatives oxythiamine or benfo-oxythiamine.
Highlights
The ability to determine biomarkers in macrophages in the blood using flow cytometry has opened the doors to a completely new form of non-invasive diagnostics (“liquid biopsy”), with which it is possible to detect tumors earlier and characterize their malignancy
The very low specificity of the biomarker prostate specific antigen (PSA), which is used for the detection of prostate cancer, has led to many false positive results and concomitant considerable problems [8]
Small benign tumors and small malignancies can be not detected with tumor markers, which are determined in the blood/serum, because they release relatively small amounts of a biomarker, which will greatly be diluted in blood volume so that no significant increase in the concentration of biomarkers in the blood/serum is measurable
Summary
The ability to determine biomarkers in macrophages in the blood using flow cytometry has opened the doors to a completely new form of non-invasive diagnostics (“liquid biopsy”), with which it is possible to detect tumors earlier and characterize their malignancy. Through a “pan-cancer test”, malignancies can be detected through the presence of two biomarkers that indicate fundamental biophysical processes and are changed in all forms of malignancies [1,2] This allows medical professionals to assess the success of a surgical tumor removal [3] as well as detect recurrences early on [4], so that courses of therapy may be monitored better. In contrast to the initial diagnosis of malignancies, biomarkers such as PSA, provide significantly better clinical information when used for the purpose of therapy monitoring and detection of return of cancer (recurrence) This allows the biomarker PSA, which is no tumor marker, but a tissue-specific marker, the detection of a return of prostate cancer, when previously the prostate was removed (prostatectomy). Small benign tumors and small malignancies can be not detected with tumor markers, which are determined in the blood/serum, because they release relatively small amounts of a biomarker, which will greatly be diluted in blood volume so that no significant increase in the concentration of biomarkers in the blood/serum is measurable
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