Diagnostic and Therapeutic Potential of Circulating-Free DNA and Cell-Free RNA in Cancer Management

Abstract

Over time, molecular biology and genomics techniques have been developed to speed up the early diagnosis and clinical management of cancer. These therapies are often most effective when administered to the subset of malignancies harboring the target identified by molecular testing. Important advances in applying molecular testing involve circulating-free DNA (cfDNA)- and cell-free RNA (cfRNA)-based liquid biopsies for the diagnosis, prognosis, prediction, and treatment of cancer. Both cfDNA and cfRNA are sensitive and specific biomarkers for cancer detection, which have been clinically proven through multiple randomized and prospective trials. These help in cancer management based on the noninvasive evaluation of size, quantity, and point mutations, as well as copy number alterations at the tumor site. Moreover, personalized detection of ctDNA helps in adjuvant therapeutics and predicts the chances of recurrence of cancer and resistance to cancer therapy. Despite the controversial diagnostic values of cfDNA and cfRNA, many clinical trials have been completed, and the Food and Drug Administration has approved many multigene assays to detect genetic alterations in the cfDNA of cancer patients. In this review, we underpin the recent advances in the physiological roles of cfDNA and cfRNA, as well as their roles in cancer detection by highlighting recent clinical trials and their roles as prognostic and predictive markers in cancer management.

False Positives in Brucellosis Serology: Wrong Bait and Wrong Pond?

“…Although Mandel and Mëtais identified the cfDNA as early as 1948 [ 102 ], the concept of its use as analyte, applied in minimally invasive or non-invasive, rapid, sensitive, and accurate diagnostic methods of various diseases, remained mostly unrecognized until the last decade of the 20th century [ 103 ]. Since then, especially in the past few years, detection of cfDNA has become the proven diagnosis of various cancerous diseases (“liquid biopsies”) [ 104 , 105 , 106 , 107 , 108 ] and non-cancerous disorders such as diabetes [ 109 ], stroke [ 110 ], systemic lupus erythematosus [ 111 ], trauma [ 112 , 113 ], rheumatoid arthritis [ 114 ], inflammation [ 115 , 116 ], allograft rejection [ 117 , 118 , 119 , 120 ], and other infections [ 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ]. As a minimally invasive method, cfDNA testing is widely used [ 121 ] in the prenatal determination of genetic disorders as an alternative to the riskier amniocentesis test.…”

Liquid biopsy for gastric cancer: Techniques, applications, and future directions

“…cfDNA typically circulates bound to proteins that shield it from degradation, and it primarily arises from cell death phenomena, including necrosis and apoptosis. Other significant sources of cfDNA include NETosis or extracellular vesicles[ 66 - 68 ]. Elevated levels of cfDNA have been observed in patients with benign lesions, inflammatory diseases, or tissue trauma[ 69 ].…”

“…It is usually found in association with extracellular vesicles and lipoprotein complexes that prevent its degradation and can be secreted by both normal and pathological cells[ 94 ]. Free RNA is unstable and degrades within seconds of incubation, requiring these vehicles for stabilization[ 66 ].…”

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

“…According to the latest data [ 17 ], the normal human plasma cfDNA concentration can be as high as 500 ng/μL. In cases of advanced cancers [ 18 , 19 , 20 ], autoimmune [ 21 , 22 , 23 , 24 , 25 ], inflammatory [ 26 ], traumatic [ 27 , 28 ], post-transplantation [ 29 ] or infectious diseases [ 30 , 31 ] usually a more increased amount is detected. In addition, cfDNA levels could also be increased, due to vigorous physical exertion (such as intense sports, e.g., half marathon, ultramarathon, TRX exercises) [ 32 , 33 ] and pregnancy [ 34 ].…”