ABSTRACT
Academic and industrial groups worldwide have reported technological advances in exosome-based cancer diagnosis and prognosis. However, the potential translation of these emerging technologies for research and clinical settings remains unknown. This work overviews the role of exosomes in cancer diagnosis and prognosis, followed by a survey on emerging exosome technologies, particularly microfluidic advances for the isolation and detection of exosomes in cancer research. The advantages and drawbacks of each of the technologies used for the isolation, detection and engineering of exosomes are evaluated to address their clinical challenges for cancer diagnosis and prognosis. Furthermore, commercial platforms for exosomal detection and analysis are introduced, and their performance and impact on cancer diagnosis and prognosis are assessed. Also, the risks associated with the further development of the next generation of exosome devices are discussed. The outcome of this work could facilitate recognizing deliverable Exo-devices and technologies with unprecedented functionality and predictable manufacturability for the next-generation of cancer diagnosis and prognosis.
Subject(s)
Biosensing Techniques , Exosomes , Neoplasms , Microfluidics , Neoplasms/diagnosis , PrognosisABSTRACT
The PR/SET domain family (PRDM) comprise a family of genes whose protein products share a conserved N-terminal PR [PRDI-BF1 (positive regulatory domain I-binding factor 1) and RIZ1 (retinoblastoma protein-interacting zinc finger gene 1)] homologous domain structurally and functionally similar to the catalytic SET [Su(var)3-9, enhancer-of-zeste and trithorax] domain of histone methyltransferases (HMTs). These genes are involved in epigenetic regulation of gene expression through their intrinsic HMTase activity or via interactions with other chromatin modifying enzymes. In this way they control a broad spectrum of biological processes, including proliferation and differentiation control, cell cycle progression, and maintenance of immune cell homeostasis. In cancer, tumor-specific dysfunctions of PRDM genes alter their expression by genetic and/or epigenetic modifications. A common characteristic of most PRDM genes is to encode for two main molecular variants with or without the PR domain. They are generated by either alternative splicing or alternative use of different promoters and play opposite roles, particularly in cancer where their imbalance can be often observed. In this scenario, PRDM proteins are involved in cancer onset, invasion, and metastasis and their altered expression is related to poor prognosis and clinical outcome. These functions strongly suggest their potential use in cancer management as diagnostic or prognostic tools and as new targets of therapeutic intervention.
Subject(s)
DNA-Binding Proteins/genetics , Histone-Lysine N-Methyltransferase/genetics , Neoplasms/etiology , Neoplasms/metabolism , Nuclear Proteins/genetics , Positive Regulatory Domain I-Binding Factor 1/genetics , Positive Regulatory Domain I-Binding Factor 1/metabolism , Transcription Factors/genetics , Animals , DNA-Binding Proteins/metabolism , Disease Susceptibility , Gene Expression Regulation, Neoplastic , Histone-Lysine N-Methyltransferase/metabolism , Humans , Multigene Family , Neoplasms/mortality , Neoplasms/pathology , Nuclear Proteins/metabolism , Prognosis , Protein Binding , Protein Interaction Domains and Motifs , Signal Transduction , Transcription Factors/metabolismABSTRACT
Despite progress in recent years, pancreatic cancer still remains a major clinical challenge. Its incidence and mortality rates have been on consistent rise underscoring the critical need for novel diagnostic, prognostic and therapeutic tools for its effective management. Recent studies have demonstrated that microRNAs (miRNAs/miRs) are deregulated in a variety of malignancies, including pancreatic cancer, and play a significant role in the initiation, progression and metastasis. Furthermore, their vital involvement in the therapeutic resistance of cancer has also been established. Hence, there has been enormous interest worldwide in investigating the roles of miRNAs in pancreatic cancer pathogenesis and exploiting their utility for clinical benefit. In this review, we summarize current knowledge on the role of miRNAs in pancreatic cancer and discuss their potential use as diagnostic and prognostic biomarkers, and as novel targets for development of effective therapeutic strategies.