REVIEWS
BIOMARKERS IN HIGH GRADE SEROUS OVARIAN CANCER
Abstract
​High-grade serous ovarian cancer (HGSC) is the most common subtype of ovarian cancer. HGSC patients typically present with advanced disease, which is often resistant to chemotherapy and recurs despite initial responses to therapy, resulting in the poor prognosis associated with this disease. There is a need to utilise biomarkers to manage the various aspects of HGSC patient care. In this review we discuss the current state of biomarkers in HGSC, focusing on the various available immunohistochemical (IHC) and blood-based biomarkers, which have been examined for their diagnostic, prognostic and theranostic potential in HGSC. These include various routine clinical IHC biomarkers such as p53, WT1, keratins, PAX8, Ki67 and p16 and clinical blood-borne markers and algorithms such as CA125, HE4, ROMA, RMI, ROCA, and others. We also discuss various components of the liquid biopsy as well as a number of novel IHC biomarkers and non-routine blood-borne biomarkers, which have been examined in various ovarian cancer studies. We also discuss the future of ovarian cancer biomarker research and highlight some of the challenges currently facing the field.
Bates
2024
CIRCULATING TUMOUR CELLS: THE GOOD, THE BAD AND THE UGLY
Abstract
This review is an overview of the current knowledge regarding circulating tumour cells (CTCs), which are potentially the most lethal type of cancer cell, and may be a key component of the metastatic cascade. The clinical utility of CTCs (the "Good"), includes their diagnostic, prognostic, and therapeutic potential. Conversely, their complex biology (the "Bad"), including the existence of CD45+/EpCAM+ CTCs, adds insult to injury regarding their isolation and identification, which in turn hampers their clinical translation. CTCs are capable of forming microemboli composed of both non-discrete phenotypic populations such as mesenchymal CTCs and homotypic and heterotypic clusters which are poised to interact with other cells in the circulation, including immune cells and platelets, which may increase their malignant potential. These microemboli (the "Ugly") represent a prognostically important CTC subset, however, phenotypic EMT/MET gradients bring additional complexities to an already challenging situation.
Bates
2023
PLATELETS, IMMUNE CELLS AND THE COAGULATION CASCADE; FRIEND OR FOE OF THE CIRCULATING TUMOUR CELL?
Abstract
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
Ward
2021
PROGNOSTIC FEATURES OF THE TUMOUR MICROENVIRONMENT IN OESOPHAGEAL ADENOCARCINOMA
Abstract
Oesophageal adenocarcinoma (OAC) is a disease with an incredibly poor survival rate and a complex makeup. The growth and spread of OAC tumours are profoundly influenced by their surrounding microenvironment and the properties of the tumour itself. Constant crosstalk between the tumour and its microenvironment is key to the survival of the tumour and ultimately the death of the patient. The tumour microenvironment (TME) is composed of a complex milieu of cell types including cancer-associated fibroblasts (CAFs) which make up the tumour stroma, endothelial cells which line blood and lymphatic vessels and infiltrating immune cell populations. These various cell types and the tumour constantly communicate through environmental cues including fluctuations in pH, hypoxia and the release of mitogens such as cytokines, chemokines and growth factors, many of which help promote malignant progression. Eventually, clusters of tumour cells such as tumour buds break away and spread through the lymphatic system to nearby lymph nodes or enter the circulation forming secondary metastasis. Collectively, these factors need to be considered when assessing and treating patients clinically. This review aims to summarise the ways in which these various factors are currently assessed and how they relate to patient treatment and outcome at an individual level.
Mcshane
2021
YB-1: THE KEY TO PERSONALISED PROSTATE CANCER MANAGEMENT?
Abstract
Y-box-binding protein 1 (YB-1) is a DNA/RNA binding protein increasingly implicated in the regulation of cancer cell biology. Normally located in the cytoplasm, nuclear localisation in prostate cancer is associated with more aggressive, potentially treatment-resistant disease. This is attributed to the ability of YB-1 to act as a transcription factor for various target genes associated with androgen receptor signalling, survival, DNA repair, proliferation, invasion, differentiation, angiogenesis and hypoxia. This review aims to examine the clinical potential of YB-1 in the detection and therapeutic management of prostate cancer.
Bates
2020
TOO MAD OR NOT MAD ENOUGH: THE DUPLICITOUS ROLE OF THE SPINDLE ASSEMBLY CHECKPOINT PROTEIN MAD2 IN CANCER
Abstract
MAD2 is an intriguing protein, which has been associated with poor survival in cancer. Depending on the organ-specific cancer, either high expression or low expression levels have been correlated with low survival rates in patients. MAD2 is also a marker of contradiction. The normal function of MAD2 is to accumulate at kinetochores and generate a wait signal preventing the cell from progressing to anaphase of the cell cycle until the spindle microtubules have correctly aligned with the kinetochores on each chromosome. This process ensures that sister chromatids segregate correctly into each new daughter cell upon cellular division. Thus, the correct function of MAD2 and this crucial cell cycle checkpoint, the spindle assembly checkpoint (SAC), is essential for faithful replicative cell division, the prevention of chromosomal abnormalities and the development of cancer. Surprisingly when MAD2 is suppressed for example through siRNA, this results in the induction of cellular senescence or cell cycle arrest. This is an inherent contradiction as normally the disbursement of MAD2 would signal to a cell that they should proceed to anaphase as spindle microtubules have correctly aligned with each chromatid for cell division. In the inverse setting; a second contradiction, high MAD2 expression in cancer patients generally correlates with abnormal chromosome number. However, in normal cells high expression of MAD2 would limit this by generating a wait signal to prevent the cell from proceeding through the cell cycle. In this review article we aim to make sense of the MADness and review the current knowledge of MAD2 and its role in cancer.