Advances in Blood-Based Screening for Cancer

Dear Colleagues,

Cancer is one of the leading causes of death worldwide, posing a huge economic burden. In the United States alone, the total annual cost of cancer care in 2015 was USD 183 billion and is estimated to exceed USD 246 billion by 2030. There has been constant progress in the understanding of cancer. Nowadays, there are more effective personalized treatments that can target not only specific tumors but specific mutations. Nevertheless, the most important prognostic factor is the stage at the time of diagnosis. Early detection has the most important impact on morbidity and mortality.

The ideal early screening test should fulfill the following criteria:

1. Non-invasive;
2. Safe;
3. Effective;
4. Repeatable;
5. Simple;
6. Relatively low cost.

In medicine, tissue is the issue; hence the novel technique of liquid biopsy (LB) has become highly relevant. LB consists of detecting proteins, RNA, DNA, and nanovesicles such as exosomes in the bloodstream and other body effluents and can potentially facilitate the diagnosis and monitoring of cancer and other diseases. LB can detect not only cell-free DNA (cfDNA) but also mutations, methylations, and copy number variants. Although LB is not routinely used, the ongoing research highlights the potential clinical applications of LBs and increases its popularity.

Notably, traditional biopsies provide information on the predominant cells in the tumor, whereas LB might have an advantage since it provides data on the entire tumor at all its sites.

LB is not restricted to blood sampling and can be obtained from other body fluids, including saliva, cerebrospinal fluid (CSF), urine, feces, etc. Thus, advances in this field will surely transform the process of early detection of malignancies.

The clinical applications of LB are broad and include screening, diagnosis, prognosis, prediction of response to treatment, and resistance. This special edition is dedicated to the early detection of cancer.

The assessment of cancer mutation profiles is fundamental to patient management and treatment decisions. One of the main challenges in tumor diagnostics and therapy is the occurrence of genomic heterogeneity in human tumors. Tissue biopsy, the standard procedure used for cancer diagnosis and a source of tissue for biomarker testing, is unable to describe tumor heterogeneity and track neoplasm evolution. In addition, tissue biopsies are limited by sample availability and, therefore, might provide only a partial characterization of the whole tumor tissue.

Knowledge of non-invasive tumor monitoring has immensely advanced since the spotting of circulating cfDNA and brought to the development of LB for the early detection of multiple types of cancer with samples easily obtained from blood and other body fluids. Moreover, LB can overcome tumor heterogeneity, which represents one of the main causes of therapeutic failure, and enables the analysis of tumor analytes, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA) microRNA (miRNA), tumor-educated platelets (TEPs), and exosomes, all of which are identified using biomarkers such as somatic point mutations, deletions, amplifications, gene fusions, DNA methylation markers, miRNAs, and proteins.

ctDNA can be used as a biomarker for the prediction, diagnosis, and prognosis of cancer due to the presence of tumor-specific genetic and epigenetic abnormalities in its sequence. Most of the studies published on the use of ctDNA in LB deal with the detection of mutations leading to resistance mechanisms, follow-up treatment, and disease response in cancer patients. As the relative amount of ctDNA in total cfDNA samples is exceedingly low, highly sensitive detection methods are required to identify ctDNA fractions in blood tests.

Exosomes are a type of extracellular nanovesicles packaged with proteins, coding and non-coding RNA, and DNA from their cell of origin. Exosomes play a significant role in exchanging molecular information between cells, including cancer cells. Clinically, exosomes isolated from the blood of cancer patients have been associated with metastasis and relapse and could serve as a diagnostic and prognostic marker and for evaluating treatment response. The isolation and analysis of exosomes in the present clinical setting are challenging and face great limitations. There is a need for more advanced research on innovative technologies in this field to facilitate a routine exosome-based LB.

At present, all acquired data from liquid biopsies are obtained from single analyte assays. Data incorporation of multiple analytes from a single blood sample through multiparametric assays would greatly impact liquid biopsy technology, improving tumor resolution and broadening the range of suitable applications.

This Special Issue welcomes basic and clinical research that highlights and discusses different approaches used in non-invasive monitoring allowing for tumor diagnosis, evaluation of the response to treatment, tumor progression, recurrence, and prognosis.

It is also of interest to receive contributions addressing new developments of ctDNA detection methods and proposing combination strategies employing multianalyte approaches, in addition to discussing specificity, sensitivity, and reproducibility of this new biopsy technology.

Dr. Shiran Shapira
Prof. Dr. Nadir Arber
Guest Editors

Manuscript Submission Information

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• liquid biopsy
• cancer
• screening
• prevention
• early detection
• tumor response