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In this blog post, we will review prostate cancer markers and what you should look for in your results. Prostate antigen marker (PSA) and p63 are the most common markers found in prostate cancer patients. The p504s immunostain is a relatively new marker that has shown promising results in early detection of prostate cancer. What is prostate cancer ? Prostate cancer is the most common type of cancer in men. It is a cancer that starts in the prostate, a small gland in the male reproductive system. The prostate is located just below the bladder and in front of the rectum. The prostate produces a fluid that helps to nourish and transport sperm during ejacu …

Our Cancer Research Club symposium series continued on Wednesday afternoon, at Royal College of Surgeons (RCSI), Dublin, Ireland. The Bouchier-Hayes lecture theatre was at maximum capacity with over 60 scientists from all major universities and Institutes in Ireland coming together to network around the theme of “The Tumor Microenvironment”.This event was organised by Dr. Tríona Ní Chonghaile & Dr. Helena Bonner from RCSI who provided a great series of lectures and invited guests.Our first speaker was Alessandra Di Grande who is a PhD student in Tríona Ní Chonghaile’s group in RCSI. Alessandra was our chosen PhD award winner. Alessandra provided a great insight into BH3 mimetic …

In 2006, upon completion of the Human Genome Project, it was discovered that nearly 8% of the human genome is made up of viral DNA. These viral remnants are composed of ancient germline infections known as human endogenous retroviruses (HERVs) which are passed on to future generations in a Mendelian fashion1–4. Although these viral elements were previously thought to be ‘junk DNA’ or DNA with no functions in the body, research has slowly been emerging over the years that show that these viral sequences play a key role in many cancers including breast cancer. Structure of the Human Endogenous Retrovirus (HERV) …

Incidence rate of Acute Lymphoblastic Leukaemia Acute lymphoblastic leukaemia (ALL) is one of the most common malignant diseases diagnosed in children. It represents nearly one third of all paediatric cancers and 74% of leukaemic disease in children from age 0-19 years. In 2010 the American Society of Cancer (ACS) predicted that 5,330 new cases of ALL would be detected and that 1,420 of these cases would result in death [Society, 2010]. Causes of ALL The cause of ALL remains largely unknown, although potential risk factors include environmental factors, inherited genetic mutations and viral exposure, howev …

By Shane Houston, PhD Candidate Queen’s University Belfast Cancer is an age old adversary of the human race. This out-of-control growth of abnormal cells has been a shadow over human health throughout history. Some of the earliest evidence of cancer stretches back to Egypt and the time of the pharaohs [1]. As time has marched on, so has our understanding of the disease, a field which came to be known as Oncology [1]. Early attempts at treating the disease most often involved surgical removal, followed by the hope the disease would not return [1]. Invariably it did. The current trend of research in cancer therapy is now leaning towards personalized medicine, a treatment approach bas …

Cell Signalling Cell signalling pathways have an important role in integrating a plethora of extracellular and intracellular signals to produce a controlled optimal output of signals, and results in the regulation of specific cellular responses. This is crucial for the homeostasis of the cell, and the deregulation of signalling pathways has been related to a number of diseases including cancer (Choudhary and Mann 2010).  Receptor signalling Cells integrate signals from the extracellular matrix by expressing specific receptors on the plasma membrane that can be activated by a specific ligand. Receptors then transduce the ex …

Shane O’Grady, PhD student, RCSI Cancer is a disease that will, unfortunately, touch all of our lives at some point, directly or indirectly. Despite decades of gradual, hard-won incremental improvements to available treatment options, survival is still strongly associated with the stage at which a tumour is first detected: patients diagnosed with stage 4 breast cancer have a 5 year survival rate approximately 4 times lower than those presenting in the clinic with a stage 1 tumour [1]. The ability to detect breast cancer at an early, more easily treated stage has been a significant contributor to improved survival rates observed in recent decades. Th …

I have been in the situation that I’m sure many of us have. I work on genes, which if you name to any right-minded individual, sound like a random string of nonsensical gibberish. So, maybe unsurprisingly, I have very little interest in writing a blog piece only about the particular genes I work on, so let’s look at AML in a wider context (and then maybe I’ll sneak in my research later). Acute myeloid leukaemia (or AML as it is more commonly known), is the most common form of acute leukaemia in adults (Eriksson et al. 2015). This disease involves the uncontrolled accumulation of progenitors, that give rise to myeloid-type white blood cells, within the bone marrow. The accumulati …

Platinum based cancer drugs Despite nearly 50% of all anti-cancer treatments being platinum-based, there is an urgent need to develop novel therapeutics beyond those currently in use.1 The first platinum-based anti-cancer chemotherapeutic, cisplatin, was granted clinical approval in 1978. Only two further platinum drugs have gained full global approval namely carboplatin and oxaliplatin.2 Although hugely successful, the widespread application and efficacy of platinum drugs are hindered by their toxic side effects, their limited activity against many human cancers and their susceptibility to acquired drug resistance.3 As a consequence, many …

By Zoe Angel, PhD Student, Ulster University Prostate cancer is now the commonest cancer in men and it is the fifth leading cause of death (1). Researchers have strived to understand its development and extraordinary progress has been made in the last 50 years. Better treatments for this disease have been developed and the outlook is steadily improving for prostate cancer patients. Despite this, significant challenges remain in prostate cancer therapy. It remains difficult to accurately predict which tumours are most aggressive and which will respond to treatment. Furthermore, chemotherapeutic approaches have mainly consisted of blocking sex ho …

Millions of people are afflicted with cancer each year. 2016 statistics for the USA alone show over half a million deaths attributed to cancer 1. We have come a long way from our early understanding of cancer, and now have highly sophisticated and personalized treatments available in the 21st century. One of the major challenges facing effective treatment is detection time. Cancer detected early has a higher chance of being cured compared to a late prognosis in most cases. Modern medicine uses several tests such as MRI and CT scans, ultrasound, pathology reports etc. to gather as much information as possible. According to American Cancer Society, it takes a minimum of a few weeks fro …

Mechanical forces are common in biological systems and dominate numerous perturbations that are relevant to human physiology and disease. Mechanobiology is a new field that evaluates the effects of physical forces on cell behavior, cell/tissue morphogenesis and diseases such as cancer. Most recently this field has matured in a way that it appears feasible to apply this approach for the identification of both disease-related signaling defects and of key determinants of chemoresistance.As a member of a group of investigators led by Elisa Giovannetti at the VU University Medical Center in Amsterdam (The Netherlands) and at Cancer Pharmacology lab, AIRC Start-Up Unit, University of Pis …

Myrna Hurtado, PhD Student, University of North Texas Health Science Center Advancements in modern medicine have resulted in significantly prolonging and also improving our quality of life. Diseases that were once major afflictions and wiping out vast populations have been almost eradicated. However, these advancements have also led us to realize how much we do not know. It is not improbable to call cancer as the plague of the 21st century. Cancer is a multifactorial disease and arises due to several characteristics acquired from DNA mutations, such as continuous proliferative signaling, resistance to cell death, and invasion and metastasis[1]. 1 …

Polo-like kinase (Plk1) Polo-like kinase (Plk1), is a serine/threonine kinase that is active during mitosis (Hamanaka et al., 1995). Its name is derived from its original characterisation as a homolog of a Drosophila mitotic kinase encoded by the Polo gene (Fenton et al., 1993; Martin et al., 2006). There are five Plk kinases identified in humans, although only Plk1 has been extensively characterised as a mitotic kinase (Martin et al., 2006; Lens et al., 2010). Polo-like Kinase family members Other members of the family have largely non-mitotic functions: Plk2 and Plk4 are involved in centriole duplication (Warnke et al., 2004; …

Oesophageal Adenocarcinoma is on the rise globally affecting more than 450,000 people worldwide (Pennathur, Gibson et al. 2013). Once diagnosed overall 5-year survival ranges from 15 % to 25 %, with the best outcomes being associated diagnosis in the early stages of cancer development (Pennathur, Gibson et al. 2013). Oesophageal Adenocarcinoma (OAC) arises from a pre malignant condition known as Barrett’s Oesophagus (BO). BO is associated with an increased risk of developing OAC compared to normal age matched controls. Barrett’s Oesophagus Barrett’s oesophagus (BO) occurs when the normal squamous epithelium of the oesophagus is replaced by …

Protein kinase B or AKT (PKB) is a serine/threonine kinase. In mammals it is comprised of 3 highly homologous isoforms PKBα (Akt1), PKBβ (Akt2), and PKBγ (Akt3) (Manning and Cantley 2007). AKT signalling is activated in response to a variety of hormones, growth factors and extracellular matrix (ECM) components. The serine/threonine kinase AKT is involved in the regulation of a number of cellular processes including cell growth, proliferation, metabolism and cell survival. AKT Signalling Activation AKTs are activated by receptor tyrosine kinases (RTKs). RTKs activate phosphatidylinositol 3-kinase (PI3K) through tyrosine phosphorylation of adaptor proteins …

HMGB1 Functional Overview High mobility group box 1 ( HMGB1), a member of the high-mobility group (HMG) family, was first identified in the thymus in 1973 and is classified as a non-histone DNA-binding protein (Goodwin et al., 1973). HMGB1, a 215 amino-acid protein, is structurally composed of two HMG-box domains, which are DNA-binding, and C-terminal tail which facilitates protein-protein interactions (Park et al., 2004; Stros et al., 2010). Nuclear HMGB1 acts as a DNA chaperone and contributes to several regulatory processes in the nucleus such as transcriptional stability, nucleosome assembly and DNA replication (Agresti et al., 2003; Reeves et a …

Thanks to the great intuitions of brilliant scientists like Louis Pasteur, Edward Jenner, Robert Koch, Emil von Behring, Gaston Leon Ramon, Albert Sabin, Jonas Salk in the past century, the world has gotten to know the super power inside every individual: THE IMMUNE SYSTEM. “Find a pathogen, isolate it, kill it and inject it in the host…… the rest is left to our immune system”. Thanks to that concept, microorganisms like Yersinia pestis, Spanish flu and many others responsible of devastating society provoking millions of deaths were finally facing the end of their days thanks to a very simple, yet new concept developed by the greatest minds of the past century“ Vaccination”. Thi …

Pancreatic cancer survival rates Despite recent advances in our understanding of this disease, pancreatic cancer is one of the world’s most lethal malignancies. Although the disease accounts for only about 3% of all cancers, it is regarded as the 7th leading cause of cancer related deaths worldwide (Siegel, R et al., 2019). Worryingly, the overall 5-year survival rate for pancreatic cancer is less than 6%; where most patients die within 3 to 8 months after diagnosis and can be regarded as the ultimate death penalty. Chemoresistance and radioresistance are leading to tumour recurrence and metastatic lesions with enhanced aggressiveness, and …

By Dr. Lisa Dwane, Postdoctoral Researcher, Royal College of Surgeons in Ireland The first link between estrogen and breast cancer was made in the late 1800s, when physician George Beatson, who correctly suspected a link between the endocrine system and breast cell proliferation, removed the ovaries of a 33-year old woman with advanced breast cancer and controlled the growth of her tumours (Clarke, 1998). The young mother astonishingly lived for four years following this surgery; an unheard miracle in an era that offered toxic chemotherapy and debilitating surgical procedures as the only options for advanced cancer. Over a century later our …

By Rachel Bleach, PhD Student, RCSI By the age of 79 years, 1 in 14 women will develop breast cancer (Global Burden of Disease Cancer 2017). Beatson reported on the utility of removing the ovaries in the treatment of advanced breast cancer in 1896, leading to the observation that estrogen is one of the driving factors in breast cancer. This discovery revolutionised the field for breast cancer treatments and since then, there has been a firm focus on estrogen ablation as a therapy (Love and Philips 2002). Initially therapies such as selective estrogen receptor modulators/degraders were developed to target the estrogen receptor (ER) protein. More rece …

LATS kinases belong to a family of proteins that, in mammals, are comprised of two isoforms, LATS1 and LATS2. Originally identified in Drosophila melanogaster as Warts kinase, LATS1 and LATS2 serine/threonine kinases have been shown to be tumour suppressors (Edwards and Munger 2004). The original homologue of LATS was described as the dlats/warts tumour suppressor in two independent screens in Drosophila (Justice et al. 1995, Xu et al. 1995). Dlats and warts encoded the same gene so in this thesis the original homologue of LATS is warts (wts). Homozygous loss of the warts gene in Drosophila formed greatly overgrown somatic cells which lead to the hypothesis that warts is a tumour suppr …

Cancer DevelopmentCancer is a group of diseases that involves abnormal cell growth resulting in malignant tumours/ malignant neoplasms. Cancer is a leading cause of morbidity, with 14 million new cases diagnosed and 8.2 million people dying from cancer in 2012 (World Health Organisation 2015). The different types of cancers are classified by the cell type they originate from. The most common cancers are breast, colorectum, lung, cervix, and stomach cancer. There are a number of risk factors that lead to cancer development such as smoking tobacco, an unbalanced diet, being overweight, alcohol use and lack of physical activity (World Health Organisation 2015) Cancer development results i …

A wide variety of cell surface receptors activate Ras GTPase, including the tyrosine receptor linked to the epidermal growth factor receptor (EGFR) (Wells 1999). Upon receptor stimulation, son of sevenless (SOS) stimulates Ras to change from GDP to GTP resulting in Ras activation (Geyer and Wittinghofer 1997).Ras GTPaseRas GTPase shuttles between inactive GDP-bound and active GTP-bound conformation (Colicelli 2004). The best characterised isoforms of Ras GTPase are K-Ras, H-Ras and N-Ras, which are demonstrated to be mutated in 30% of human tumours (Repasky et al. 2004). Activated Ras phosphorylates and activates the Ser/Thr kinase Raf. The three isoforms of Raf are B-Raf, Raf-1 and A- …