The potential of circulating nucleic acids as components of companion diagnostics for predicting and monitoring chemotherapy response

Abstract

An effective personalized medicine is associated with the ability of identifying cancer patients who respond to anticancer targeted therapies. Therefore, new companion biomarkers that facilitate drug development are urgently needed. Since clinically relevant genetic and epigenetic alterations can be detected in cell-free nucleic acids in the blood circulation of cancer patients, these molecules may be a new promising class of potential liquid biomarkers. They can be obtained in real-time from blood, and their analyses could, consequently, facilitate treatment decisions. Screening of these liquid biopsies may provide information on the aberrant signaling pathway that should be blocked by the chosen targeted therapy. This article will discuss the potential of circulating nucleic acids as therapeutics for overcoming chemotherapeutic resistance in anticancer strategies.

Keywords:

• chemotherapy
• circulating DNA
• circulating miRNA
• epigenetic alterations
• genetic alterations
• resistance
• targeted therapy

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Companion diagnostics addresses the customization of healthcare and comprises molecular analyses, medical decisions, practices and drugs being tailored to the individual cancer patient.

• Blood of cancer patients constitutes a pool of cell-free nucleic acids with tumor-associated abnormalities derived from different sources, amongst others from heterogeneous areas of the primary tumor and metastases.

• Deregulated levels of circulating nucleic acids in patient blood reflect pathological processes during the cancer development and progression and parallel with the severity of disorder.

• Circulating DNA of cancer patients carries tumor-related genetic and epigenetic alterations that may be relevant to resistance to therapy.

• miRNAs, a family of small non-coding RNAs that cause translational repression of mRNA, may be targeted agents by modulating the drug sensitivity of cancer cells.

• Detection of nucleic acids in human blood that can be cell free, protein bound or exosomal has opened up new possibilities to enhance insight into the biological behavior of the primary tumor and metastases.

• Minimally invasive blood analyses allow repetitive real-time screening of nucleic acids that may associate with tumor dynamics during drug treatment and be eligible for companion diagnostics.

• Exosomes can also be used as targeted drug delivery vehicles and be entered clinical trials for different cancers.