Challenges in cancer research and multifaceted approaches for cancer biomarker quest

Recent advances in cancer biology have subsequently led to the development of new molecularly targeted anti-cancer agents that can effectively hit cancer-related proteins and pathways. Despite better insight into genomic aberrations and diversity of cancer phenotypes, it is apparent that proteomics too deserves attention in cancer research. Currently, a wide range of proteomic technologies are being used in quest for new cancer biomarkers with effective use. These, together with newer technologies such as multiplex assays could significantly contribute to the discovery and development of selective and specific cancer biomarkers with diagnostic or prognostic values for monitoring the disease state. This review attempts to illustrate recent advances in the field of cancer biomarkers and multifaceted approaches undertaken in combating cancer.     

Metabolomics for mitochondrial and cancer studies

Metabolomics, a high-throughput global metabolite analysis, is a burgeoning field, and in recent times has shown substantial evidence to support its emerging role in cancer diagnosis, cancer recurrence, and prognosis, as well as its impact in identifying novel cancer biomarkers and developing cancer therapeutics. Newly evolving advances in disease diagnostics and therapy will further facilitate future growth in the field of metabolomics, especially in cancer, where there is a dire need for sensitive and more affordable diagnostic tools and an urgency to develop effective therapies and identify reliable biomarkers to predict accurately the response to a therapy. Here, we review the application of metabolomics in cancer and mitochondrial studies and its role in enabling the understanding of altered metabolism and malignant transformation during cancer growth and metastasis. The recent developments in the area of metabolic flux analysis may help to close the gap between clinical metabolomics research and the development of cancer metabolome. In the era of personalized medicine with more and more patient specific targeted therapies being used, we need reliable, dynamic, faster, and yet sensitive biomarkers both to track the disease and to develop and evolve therapies during the course of treatment. Recent advances in metabolomics along with the novel strategies to analyze, understand, and construct the metabolic pathways opens this window of opportunity in a very cost-effective manner.     

用于肿瘤治疗的免疫检查点抑制剂相关预测生物标志物的研究进展

恶性肿瘤是严重威胁人类健康和社会发展的疾病。传统的肿瘤治疗方法如手术、放疗、化疗和靶向治疗等不能完全满足临床治疗的需求,新兴的免疫治疗成为了肿瘤治疗领域的研究热点。免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)作为一种肿瘤免疫治疗方法,已获批用于治疗多种肿瘤,如肺癌、肝癌、胃癌和结直肠癌等。然而,ICIs在临床使用过程中,只有少数患者会出现持久反应,一些患者还会出现耐药和不良反应。因此,预测生物标志物的鉴定和开发对提高ICIs的治疗效果至关重要。肿瘤ICIs预测生物标志物主要包括肿瘤生物标志物、肿瘤微环境生物标志物、循环相关生物标志物、宿主环境生物标志物以及组合生物标志物等,对患者筛查、个体化治疗和预后评估具有重要意义。本文就肿瘤ICIs治疗预测生物标志物的前沿进展作一综述。     

Pathway mapping and development of disease‐specific biomarkers: protein‐based network biomarkers

It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network‐based identification of biomarkers. The network biomarkers and dynamic network biomarkers (DNBs) represent new types of biomarkers with protein–protein or gene–gene interactions that can be monitored and evaluated at different stages and time‐points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue‐generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases‐specific, stage‐specific, severity‐specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed.     

NASA Radiation Biomarker Workshop, September 27-28, 2007

A summary is provided of presentations and discussions at the NASA Radiation Biomarker Workshop held September 27-28, 2007 at NASA Ames Research Center in Mountain View, CA. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including those exposed during long-duration space travel. Topics discussed included the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage after large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. A summary of conclusions is provided at the end of the report.     

Proteomic cancer biomarkers from discovery to approval: it’s worth the effort

The current landscape of cancer biomarkers is changing rapidly, with new and exciting developments. With the advances of proteomic technologies, many potential cancer biomarkers have been discovered. However, the number of new cancer biomarkers cleared or approved by the US FDA is rather limited. Although technological advances are important, clearly defining intended use, good study design and appropriate patient specimens are critical for the success of FDA approval. While obtaining FDA clearance/approval for newly developed and clinically useful cancer biomarkers has been slow, the reward for patient care could be enormous.     

Biomarkers for Primary Sjgren's Syndrome

Primary Sjo¨gren's syndrome(p SS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of p SS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in p SS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjo¨gren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions.     

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers

Gastric and esophageal cancers are as main cancers of the gastrointestinal (GI) tract, which are associated with poor diagnosis and survival. Several efforts were made in the past few decades to finding effective therapeutic approaches, but these approaches had several problems. Finding new biomarkers is a critical step in finding new approaches for the treatment of these cancers. Finding new biomarkers that cover various aspects of the diseases could provide a choice of suitable therapies and better monitoring of patients with these cancers. Among several biomarkers tissue specific and circulating microRNAs (miRNAs) have emerged as powerful candidates in the diagnosis of gastric and esophageal cancers. MiRNAs are small noncoding single‐stranded RNA molecules that are found in the blood and regulate gene expression. These have numerous characteristics that make them suitable for being used as ideal biomarkers in cancer diagnosis. Research has indicated that the level and profile of miRNA in serum and plasma are very high. They are potentially noninvasive and sensitive enough to detect tumors in their primary stages of infection. Multiple lines of evidence indicate that the presence, absence, or deregulation of several circulating miRNAs (i.e., let‐7a, miR‐21, miR‐93, miR‐192a, miR‐18a, and miR‐10b for gastric cancer, and miR‐21, miR‐375, miR‐25‐3p, miR‐151a‐3p, and miR‐100‐3p for esophageal cancer) are associated with initiation and progression of gastric and esophageal cancers. The aim of this review is to highlight the recent advances in the roles of miRNAs in diagnosis and treatment of gastric and esophageal cancers.     

Potential use of inflammation and early immunological event biomarkers in assessing vaccine safety

Highly effective vaccines have traditionally been designed in a rather empirical way, often with incomplete understanding of their mode of action. Full assessment of efficacy and reactogenicity takes time and, as a result, vaccine introduction to the market is usually slow and expensive. In addition, in rare cases, unacceptable reactogenicity may only become apparent after years of development or even widespread use. However, recent advances in cell biology and immunology offer a range of new technologies and systems for identifying biological responses or “biomarkers” that could possibly be used to evaluate and predict efficacy and safety during vaccine development and post-marketing surveillance.This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the potential use of biomarkers to assess vaccine safety which was held in Baltimore, Maryland, USA, from 10 to 11 May 2012 and organized by the International Association for Biologicals (IABS). The conference focused particularly on determining which biomarkers might relate to vaccine efficacy and reactogenicity and whether our knowledge base was sufficiently robust at this time for the data to be used for decision-making. More information on the conference output can be found on the IABS website, http://www.iabs.org/.     

污染土壤的生物标记物研究进展

生物标记物是指示环境中污染物危害效应的生物信号。利用生物标记物进行污染土壤的检测和定量分析是最可行的方法之一。本文主要综述了近年来一些典型的、指示土壤污染的几类生物标记物 (如细胞色素P4 5 0加氧酶系统、细胞抗氧化酶及DNA指纹技术 )的最新研究进展 ,并探讨了生物标记物在污染土壤修复效果评价及其早期诊断方面的应用前景。     

Proteomics: a new way to improve human African trypanosomiasis diagnosis?

African trypanosomiases, including the human disease referred to as ‘sleeping sickness’ and the animal diseases such as nagana, surra and dourine, are neglected vector-borne diseases that after years of research still need improved diagnosis and chemotherapy. Advances in proteomics offer new tools to define biomarkers, whose expression may reflect host–parasite interactions occurring during the infection. In this review, the authors first describe the current diagnostic tools used to detect a trypanosome infection during field surveys, and then discuss their interests, limits and further evolutions. The authors also report on the contribution of molecular diagnostics, and the recent advances and developments that make it suitable for fieldwork. The authors then explore the recent uses of proteomics technology to define host and parasite biomarkers that allow detection of the infection, the power and constraints of the technology. The authors conclude by discussing the urgent need to use the biomarkers discovered in order to develop tools to improve trypanosomiasis control in the near future.     

New Insight into Neurodegeneration: the Role of Proteomics

Recent advances within the field of proteomics, including both upstream and downstream protocols, have fuelled a transition from simple protein identification to functional analysis. A battery of proteomics approaches is now being employed for the analysis of protein expression levels, the monitoring of cellular activities and for gaining an increased understanding into biochemical pathways. Combined, these approaches are changing the way we study disease by allowing accurate and targeted, large scale protein analysis, which will provide invaluable insight into disease pathogenesis. Neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), prion disease, and other diseases that affect the neuromuscular system, are a leading cause of disability in the aging population. There are no effective intervention strategies for these disorders and diagnosis is challenging as it relies primarily on clinical symptomatic features, which often overlap at early stages of disease. There is, therefore, an urgent need to develop reliable biomarkers to improve early and specific diagnosis, to track disease progression, to measure molecular responses towards treatment regimes and ultimately devise new therapeutic strategies. To accomplish this, a better understanding of disease mechanisms is needed. In this review we summarize recent advances in the field of proteomics applicable to neurodegenerative disorders, and how these advances are fueling our understanding, diagnosis, and treatment of these complex disorders.     

Single-cell analysis of tumors: Creating new value for molecular biomarker discovery of cancer stem cells and tumor-infiltrating immune cells

Biomarker-driven individualized treatment in oncology has made tremendous progress through technological developments, new therapeutic modalities and a deeper understanding of the molecular biology for tumors, cancer stem cells and tumor-infiltrating immune cells. Recent technical developments have led to the establishment of a variety of cancer-related diagnostic, prognostic and predictive biomarkers. In this regard, different modern OMICs approaches were assessed in order to categorize and classify prognostically different forms of neoplasia. Despite those technical advancements, the extent of molecular heterogeneity at the individual cell level in human tumors remains largely uncharacterized. Each tumor consists of a mixture of heterogeneous cell types. Therefore, it is important to quantify the dynamic cellular variations in order to predict clinical parameters, such as a response to treatment and or potential for disease recurrence. Recently, single-cell based methods have been developed to characterize the heterogeneity in seemingly homogenous cancer cell populations prior to and during treatment. In this review, we highlight the recent advances for single-cell analysis and discuss the challenges and prospects for molecular characterization of cancer cells, cancer stem cells and tumor-infiltrating immune cells.     

Current advances in tumor proteomics and candidate biomarkers for hepatic cancer

Tumor proteomics apply proteomics techniques to tumor biological research, mainly by screening candidate biomarkers for early tumor diagnosis, prognosis and treatment. Hepatocellular carcinoma (HCC) is a type of malignant tumor with one of the highest death rates in the world. With the advent of the post-genomic age, tumor biological research developing the technology of proteomics has become a major focus of researchers. The discovery of novel candidate biomarkers is one of crucial problems for the early diagnosis of HCC. In general, there are three distinct types of candidate biomarkers for HCC based on different areas: biochemical biomarkers, antigenic biomarkers and epigenetic biomarkers. This review mainly discusses current advances in the problems and prospects of candidate biomarker for the early diagnosis of HCC, discovered by technologies of tumor proteomics.     

Targeted quantitation of CVD-linked plasma proteins for biomarker verification and validation

Despite significant advances in treatment, cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in developed and developing countries. Judicious monitoring of common risk factors has been unable to control this global epidemic, necessitating novel biomarkers for improved screening and earlier disease detection and management. Although numerous plasma proteins have been associated with CVD, only a few of these potential biomarkers have been validated for clinical use. Here we review the quantitative proteomic methods used to verify and validate new biomarker candidates in human plasma. These methods center on a bottom-up approach involving multiple or selected reaction monitoring, for targeted detection, with stable isotope-labeled standards, for peptide normalization. Also included are a discussion of future strategies for improved CVD protein biomarker verification and validation, recommendations for method translation to the clinic, and future projections for protein biomarker research.     

Serum-based protein biomarkers for detection of lung cancer

Lung cancer is one of the most common cancers in terms of both incidence and mortality.The major reasons for the increasing number of deaths from lung cancer are late detection and lack of effective therapies. To improve our understanding of lung cancer biology, there is urgent need for blood-based, non-invasive molecular tests to assist in its detection in a cost-effective manner at an early stage when curative interventions are still possible. Recent advances in proteomic technology have provided extensive, high throughput analytical tools for identification, characterization and functional studies of proteomes. Changes in protein expression patterns in response to stimuli can serve as indicators or biomarkers of biological and pathological processes as well as physiological and pharmacological responses to drug treatment, thus aiding in early diagnosis and prognosis of disease. However, only a few biomarkers have been approved by the FDA to date for screening and diagnostic purposes. This review provides a brief overview of currently available proteomic techniques, their applications and limitations and the current state of knowledge about important serum biomarkers in lung cancer and their potential value as prognostic and diagnostic tools.     

Insights into predicting diabetic nephropathy using urinary biomarkers

Diabetic nephropathy (DN) is a serious complication of diabetes caused by changes in the structure and function of the kidneys. It is important to detect diagnostic biomarkers of DN at an early stage, in which the drug can slow the loss of kidney function and prevent disease progression. In recent years, a variety of biological markers related to DN have been discovered, which is of great significance for predicting the occurrence and development of diseases. Due to the simplicity of non-invasive collection, urine is an ideal biological sample for the discovery of new biomarkers of kidney disease. We reviewed some new urinary biomarkers related to early DN patients, including urinary proteins, peptides, and exosomes biomarkers. We also highlight the proteins associated with tubular damage, glomerular damage, inflammation and oxidative stress marker. Despite the promise of these new urinary biomarkers, we next proposed a review of the most recent publications reporting on larger cohorts, focusing on those that aim at qualification or validation. This review provides important data to better understand biomarkers related to the pathophysiology of DN, and these markers have been increasingly studied for disease progression to provide effective human treatment.     

Functional relationship and gene ontology classification of breast cancer biomarkers

Breast cancer is a complex disease that still imposes a significant healthcare burden on women worldwide. The etiology of breast cancer is not known but significant advances have been made in the area of early detection and treatment. The advent of advanced molecular biology techniques, mapping of the human genome and availability of high throughput genomic and proteomic strategies opens up new opportunities and will potentially lead to the discovery of novel biomarkers for early detection and prognostication of breast cancer. Currently, many biomarkers, particularly the hormonal and epidermal growth factor receptors, are being utilized for breast cancer prognosis. Unfortunately, none of the biomarkers in use have sufficient diagnostic, prognostic and/or predictive power across all categories and stages of breast cancer. It is recognized that more useful information can be generated if tumors are interrogated with multiple markers. But choosing the right combination of biomarkers is challenging, because 1) multiple pathways are involved, 2) up to 62 genes and their protein products are potentially involved in breast cancer-related mechanisms and 3) the more markers evaluated, the more the time and cost involved. This review summarizes the current literature on selected biomarkers for breast cancer, discusses the functional relationships, and groups the selected genes based on a Gene Ontology classification.