Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using “liquid biopsies” to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occur-ring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop bio-markers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the po-tential to transform clinical pathology practice by stand-ardising the interpretation of the tissue morphology.

Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of ∼22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 3′ untranslated region (3′-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as ‘rare’ due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).

Epithelial ovarian carcinoma (EOC) is the eighth most common cancer in women and the leading cause of gynaecological cancer death, predominantly due to the absence of effective screening tools, advanced stage at diagnosis, and high rates of recurrence. Circulating tumour cells (CTCs), a rare subset of tumour cells that disseminate from a tumour and migrate into the circulation, play a pivotal role in the metastatic cascade, and therefore hold promise as biomarkers for disease monitoring and prognostication. Exploring CTCs from liquid biopsies is an appealing approach for research and clinical practice, given it is minimally invasive, facilitates serial sampling and enables the capture of the entire spectrum of cancer cells circulating in the blood. The prognostic utility of CTC enumeration has been FDA-approved for clinical use in metastatic breast, prostate, and colorectal cancers. However, the unique biology of EOC, discussed herein, compounds the detection and characterisation complexities already inherent in CTC research, consequently hindering progress towards clinical applications. The aim of this review is to provide an overview of both the biological and clinical challenges encountered in harnessing the power of CTCs in EOC.