Salivary exosomes: A theranostics secret of oral cancer – Correspondence

Dear Editor The survival period of individuals with oral cancers is very poor owing to their late diagnosis and there is no improvement in the recent period despite advances in early diagnosis [1]. To date, there are no routine cancer screening programs or tests for oral cavity and oropharyngeal cancers. However, many premalignant conditions of the oropharynx are detected during the routine examination by a dentist or during self-examination by the individual [1]. Early detection of oral cancer is an important factor in preventing physical, psychological, and financial loss to patients and enhances the success rate with effective management. Early diagnosis of oral cancer involves methods such as histopathological examination, staining, and biopsy techniques such as liquid biopsy that allows timely and appropriate treatment to be initiated, thereby improving the survival rate by up to 90% [2]. The current decade has seen advances in diagnostic methods utilizing molecular signatures such as exosomes that are involved in cellular communication and play a vital role in health or disease states including oral cancers. Exosomes transport multiple biological active molecules such as DNA, RNA (mRNA, miRNA), protein, and lipid which dynamically influence cancer development and progression [3]. In oral cancer, tumor-derived exosomes influence uncontrol cell growth (miRNA, glycan), reprogramme immune system (PDL1, enhance immune cells apoptosis, reduce anticancer cytotoxicity, angiogenesis (miRNAs), metastasis (miRNA, proteins), EMT (fibronectin), organs specific metastasis (intragrain), drug resistance (miRNAs, proteins), and cancer stem cell development (miRNAs, protein) [4,5]. However, salivary exosomes remain an unexplored side of liquid biopsy for oral cancer screening and it is a versatile source of oral cancer theranostics [6]. In salivary exosomes, miRNA-365 serves as a biomarker in oral squamous cell carcinoma (OSCC) which accounts for 90% of oral cancer [7]. Other potential exosomal biomarkers being investigated for OSCC include miRNA-125, miRNA-200a, miRNA-21, miRNA145, miRNA-200a, miRNA-93, miRNA-375, miR-184, miR-139-5p, and miRNA-31. Apart from exosomal miRNAs, surface markers such as CD63 expression patterns also play a signature role in oral cancer diagnosis. Recent research combining exosome technology with nanoplatforms by exploiting methods such as microfluidics, flow cytometry, electrochemical analysis, magnetic nano component associated exosomes sensor, surface resonance sensor, and nanoplasmonic sensor, the cancer diagnostics is been drawn into newer dimensions to develop a promising, cost-efficient, sensitive, and efficient diagnostic ecosystem through cancer exosome profiling [8]. Apart from the diagnostics, exosomes are being investigated as a cargo delivery system to tailor precision therapy with the least systemic toxicity, enhanced bioavailability, biological barrier crossing ability, less immune rejection, and target-specificity. The resistance mechanism of oral cancers to traditional therapeutics involves generation of drug-metabolizing enzymes, genetic and epigenetic mutations, alteration of signaling pathways, and immunogenicity to therapeutic agents [9]. Current research to counteract these resistant mechanisms may be strengthened with the use of salivary exosomes as a conduit for therapeutic cellular transformation. Saliva acts as a major communication channel in oral cancers and the exosomes in them could be utilized as a potential tool for cancer theranostics [10]. Research on salivary exosomes would aid not only in understanding of oral cancers but also supports unfolding of complex interplay in formation of cancer stem cells, and their resistance mechanisms to traditional chemo-immuno-therapy regimens currently employed [4–10]. Fig. 1 shows the potential ways in which salivary exosomes could be utilized in the diagnosis and management of oral cancers.Fig. 1.: Potential ways in which salivary exosomes are utilized in the diagnosis and treatment of oral cancers (created with permission from “bioRender.com”).Provenance and peer review Not commissioned, internally peer-reviewed. International journal of surgery author disclosure form The following additional information is required for submission. Please note that failure to respond to these questions/statements will mean your submission will be returned. If you have nothing to declare in any of these categories, then this should be stated. Please state whether ethical approval was given, by whom and the relevant Judgement's reference number Not applicable as no animal study was conducted. Please state any sources of funding for your research No funding. Author contribution Anand Krishnan: Conceptualization, Data curation, Writing-Original draft preparation, Writing- Reviewing, Editing and Supervision. Bikramjit Bhattacharya:Writing-Reviewing and Editing. Debashmita Mandal: Writing-Reviewing and Editing, Visualization. Rajib Dhar: Writing-Reviewing and Visualization. Sathish Muthu: Writing- Reviewing, Visualization and Editing. Research registration Unique Identifying number (UIN) 1. Name of the registry: Not applicable. 2. Unique Identifying number or registration ID: Not applicable. 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable. Guarantor Anand Krishnan. Availability of data and materials The data in this correspondence article is not sensitive in nature and is accessible in the public domain. The data is therefore available and not of a confidential nature. Declaration of competing interest Authors declare that they have no conflicts of interest.