Cancer proteomics: many technologies, one goal

A major goal of the National Cancer Institute is to alleviate patient pain, suffering and death associated with cancer by the year 2015. This goal does not insinuate a cure for cancer, but rather the development of diagnostics and therapeutics that will eventually decrease cancer morbidity and mortality. A part of meeting this goal is to leverage the enormous data-gathering capabilities of proteomic technologies to discover disease-specific biomarkers in serum, plasma, urine, tissues and other biologic samples. The rapid advance in available technologies that have been spurred by the -omics era, has enabled biologic samples to be surveyed for biomarkers in ways never before possible. However, it is not yet clear which specific technologies will be the most successful. Therefore, proteomic laboratories within the National Cancer Institute are taking a multipronged approach to identify disease-specific biomarkers. This review discusses some of these approaches in their context of meeting the National Cancer Institute's 2015 goal.     

Role of oncoproteomics in the personalized management of cancer

Oncoproteomics is the term used to describe the application of proteomic technologies in oncology and parallels the related field of oncogenomics. It is now contributing to the development of personalized management of cancer. Proteomic technologies are used for the identification of biomarkers in cancer, which will facilitate the integration of diagnosis and therapy of cancer. Molecular diagnostics, laser capture microdissection and protein biochips are among the technologies that are having an important impact on oncoproteomics. The discovery of protein patterns developed by the US Food and Drug Administration/National Cancer Institute Clinical Proteomics Program is capable of distinguishing cancer and disease-free states with high sensitivity and specificity and will also facilitate the development of personalized therapy of cancer. Examples of application are given for breast and prostate cancer and a selection of companies and their collaborations that are developing application of proteomics to personalized treatment of cancer are discussed. Continued refinement of techniques and methods to determine the abundance and status of proteins in vivo holds great promise for the future study of normal cells and the pathology of associated neoplasms. Personalized cancer therapy is expected to be in the clinic by the end of the first decade of the 21st century.     

Role of oncoproteomics in the personalized management of cancer

Oncoproteomics is the term used to describe the application of proteomic technologies in oncology and parallels the related field of oncogenomics. It is now contributing to the development of personalized management of cancer. Proteomic technologies are used for the identification of biomarkers in cancer, which will facilitate the integration of diagnosis and therapy of cancer. Molecular diagnostics, laser capture microdissection and protein biochips are among the technologies that are having an important impact on oncoproteomics. The discovery of protein patterns developed by the US Food and Drug Administration/National Cancer Institute Clinical Proteomics Program is capable of distinguishing cancer and disease-free states with high sensitivity and specificity and will also facilitate the development of personalized therapy of cancer. Examples of application are given for breast and prostate cancer and a selection of companies and their collaborations that are developing application of proteomics to personalized treatment of cancer are discussed. Continued refinement of techniques and methods to determine the abundance and status of proteins in vivo holds great promise for the future study of normal cells and the pathology of associated neoplasms. Personalized cancer therapy is expected to be in the clinic by the end of the first decade of the 21st century.     

Cancer Proteomics and the Elusive Diagnostic Biomarkers

Despite progress in genomic and proteomic technology and applications, the validation of cancer biomarkers of use as clinical early detection diagnostics has remained elusive. As described in this brief viewpoint, there are now recognized to be many types of clinical biomarkers and proteomic analyses, particularly when combined with other ‘omic analyses, have been effective in many such biomarker identifications. However, in the area of early diagnosis of cancers, the problems associated with the conversion from identification to diagnostic have largely not been overcome. Notably, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), has been particularly successful in refining the analytical steps needed to tackle this challenging issue and has provided positive insight into how to solve many of the underlying problems. The potential for developing clinical diagnostics for early detection of highly lethal cancers and possible new therapeutic strategies through proteomic analyses, as seen through these CPTAC successes, is more promising than ever.     

Urinary proteomic profiling for diagnostic bladder cancer biomarkers

The ability to detect and monitor bladder cancer in noninvasively obtained urine samples is a major goal. While a number of protein biomarkers have been identified and commercially developed, none have greatly improved the accuracy of sample evaluation over invasive cystoscopy. The ongoing development of high-throughput proteomic profiling technologies will facilitate the identification of molecular signatures that are associated with bladder disease. The appropriate use of these approaches has the potential to provide efficient biomarkers for the early detection and monitoring of recurrent bladder cancer. Identification of disease-associated proteins will also advance our knowledge of tumor biology, which, in turn, will enable development of targeted therapeutics aimed at reducing morbidity from bladder cancer. In this article, we focus on the accumulating proteomic signatures of urine in health and disease, and discuss expected future developments in this field of research.     

Advanced proteomic technologies for cancer biomarker discovery

Proteomic technologies have experienced major improvements in recent years. Such advances have facilitated the discovery of potential tumor markers with improved sensitivities and specificities for the diagnosis, prognosis and treatment monitoring of cancer patients. This review will focus on four state-of-the-art proteomic technologies, namely 2D difference gel electrophoresis, MALDI imaging mass spectrometry, electron transfer dissociation mass spectrometry and reverse-phase protein array. The major advancements these techniques have brought about and examples of their applications in cancer biomarker discovery will be presented in this review, so that readers can appreciate the immense progress in proteomic technologies from 1997 to 2008. Finally, a summary will be presented that discusses current hurdles faced by proteomic researchers, such as the wide dynamic range of protein abundance, standardization of protocols and validation of cancer biomarkers, and a 5-year view of potential solutions to such problems will be provided.     

Host-pathogen interactions: a proteomic view

Host-pathogen interactions reflect the balance of host defenses and pathogen virulence mechanisms. Advances in proteomic technologies now afford opportunities to compare protein content between complex biologic systems ranging from cells to animals and clinical samples. Thus, it is now possible to characterize host-pathogen interactions from a global proteomic view. Most reports to date focus on cataloging protein content of pathogens and identifying virulence-associated proteins or proteomic alterations in host response. A more in-depth understanding of host-pathogen interactions has the potential to improve our mechanistic understanding of pathogenicity and virulence, thereby defining novel therapeutic and vaccine targets. In addition, proteomic characterization of the host response can provide pathogen-specific host biomarkers for rapid pathogen detection and characterization, as well as for early and specific detection of infectious diseases. A review of host-pathogen interactions focusing on proteomic analyses of both pathogen and host will be presented. Relevant genomic studies and host model systems will be also be discussed.     

Host–pathogen interactions: a proteomic view

Host–pathogen interactions reflect the balance of host defenses and pathogen virulence mechanisms. Advances in proteomic technologies now afford opportunities to compare protein content between complex biologic systems ranging from cells to animals and clinical samples. Thus, it is now possible to characterize host–pathogen interactions from a global proteomic view. Most reports to date focus on cataloging protein content of pathogens and identifying virulence-associated proteins or proteomic alterations in host response. A more in-depth understanding of host–pathogen interactions has the potential to improve our mechanistic understanding of pathogenicity and virulence, thereby defining novel therapeutic and vaccine targets. In addition, proteomic characterization of the host response can provide pathogen-specific host biomarkers for rapid pathogen detection and characterization, as well as for early and specific detection of infectious diseases. A review of host–pathogen interactions focusing on proteomic analyses of both pathogen and host will be presented. Relevant genomic studies and host model systems will be also be discussed.     

The rising incidence of testicular cancer among young men in Canada,data from 1971–2015

BackgroundTesticular cancer is the most common malignancy among young men aged 15–44 in Canada. The goal of this analysis was to examine age-period-cohort effects of testicular cancer incidence between 1971 and 2015.MethodsData were collected from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Birth cohort models were fit using the National Cancer Institute’s web tool. Incidence annual percent changes were estimated using NCI’s Joinpoint Regression Program.ResultsIncidence of testicular cancer in Canada has increased steadily since 1971. A birth cohort effect was observed for men born in the years after 1945. The rate of testicular cancer peaks at age 35 and drops off with increasing age.ConclusionIncidence of testicular cancer has risen dramatically in Canada in recent decades and the cohort effect indicates the need to investigate exposures that have increased since 1945 and that may affect development in young men.     

Cancer proteomics

Conclusion The future of cancer diagnostics will be based on a panel of proteomic biomarkers. They could be used to detect cancer at an early stage, to predict and to direct therapies. Enzymes and related proteins are important biological molecules, which could serve as cancer biomarkers. These biomarkers could be intact or fragments of proteins. The challenge is to be able to find and validate these potential biomarkers as clinical diagnostics. With the advances in proteomic technologies, we are closer than ever to find these “new” enzyme molecules or fragments. The translation of newly discovered biomarkers could provide an opportunity to revolutionize the era of personalized medicine.     

Nanoparticles: potential biomarker harvesters

A previously untapped bank of information resides within the low molecular weight proteomic fraction of blood. Intensive efforts are underway to harness this information so that it can be used for early diagnosis of diseases such as cancer. The physicochemical malleability and high surface areas of nanoparticle surfaces make them ideal candidates for developing biomarker harvesting platforms. Given the variety of engineering strategies afforded through nanoparticle technologies, a significant goal is to tailor nanoparticle surfaces to selectively bind a subset of biomarkers, sequestering them for later study using high sensitivity proteomic tests. To date, applications of nanoparticles have largely focused on imaging systems and drug delivery vectors. As such, biomarker harvesting is an underutilized application of nanoparticle technology and is an area of nanotechnology research that will likely undergo substantial growth.     

Mass spectrometry-based expression profiling of clinical prostate cancer

The maturation of MS technologies has provided a rich opportunity to interrogate protein expression patterns in normal and disease states by applying expression protein profiling methods. Major goals of this research strategy include the identification of protein biomarkers that demarcate normal and disease populations, and the identification of therapeutic biomarkers for the treatment of diseases such as cancer (Celis, J. E., and Gromov, P. (2003) Proteomics in translational cancer research: Toward an integrated approach. Cancer Cell 3, 9-151). Prostate cancer is one disease that would greatly benefit from implementing MS-based expression profiling methods because of the need to stratify the disease based on molecular markers. In this review, we will summarize the current MS-based methods to identify and validate biomarkers in human prostate cancer. Lastly, we propose a reverse proteomic approach implementing a quantitative MS research strategy to identify and quantify biomarkers implicated in prostate cancer development. With this approach, the absolute levels of prostate cancer biomarkers will be identified and quantified in normal and diseased samples by measuring the levels of native peptide biomarkers in relation to a chemically identical but isotopically labeled reference peptide. Ultimately, a centralized prostate cancer peptide biomarker expression database could function as a repository for the identification, quantification, and validation of protein biomarker(s) during prostate cancer progression in men.     

Human saliva proteome analysis and disease biomarker discovery

Human saliva is an attractive body fluid for disease diagnosis and prognosis because saliva testing is simple, safe, low-cost and noninvasive. Comprehensive analysis and identification of the proteomic content in human whole and ductal saliva will not only contribute to the understanding of oral health and disease pathogenesis, but also form a foundation for the discovery of saliva protein biomarkers for human disease detection. In this article, we have summarized the proteomic technologies for comprehensive identification of proteins in human whole and ductal saliva. We have also discussed potential quantitative proteomic approaches to the discovery of saliva protein biomarkers for human oral and systemic diseases. With the fast development of mass spectrometry and proteomic technologies, we are enthusiastic that saliva protein biomarkers will be developed for clinical diagnosis and prognosis of human diseases in the future.     

A reagent resource to identify proteins and peptides of interest for the cancer community: a workshop report

On the basis of discussions with representatives from all sectors of the cancer research community, the National Cancer Institute (NCI) recognizes the immense opportunities to apply proteomics technologies to further cancer research. Validated and well characterized affinity capture reagents (e.g. antibodies, aptamers, and affibodies) will play a key role in proteomics research platforms for the prevention, early detection, treatment, and monitoring of cancer. To discuss ways to develop new resources and optimize current opportunities in this area, the NCI convened the "Proteomic Technologies Reagents Resource Workshop" in Chicago, IL on December 12-13, 2005. The workshop brought together leading scientists in proteomics research to discuss model systems for evaluating and delivering resources for reagents to support MS and affinity capture platforms. Speakers discussed issues and identified action items related to an overall vision for and proposed models for a shared proteomics reagents resource, applications of affinity capture methods in cancer research, quality control and validation of affinity capture reagents, considerations for target selection, and construction of a reagents database. The meeting also featured presentations and discussion from leading private sector investigators on state-of-the-art technologies and capabilities to meet the user community's needs. This workshop was developed as a component of the NCI's Clinical Proteomics Technologies Initiative for Cancer, a coordinated initiative that includes the establishment of reagent resources for the scientific community. This workshop report explores various approaches to develop a framework that will most effectively fulfill the needs of the NCI and the cancer research community.     

Human saliva proteome analysis and disease biomarker discovery

Human saliva is an attractive body fluid for disease diagnosis and prognosis because saliva testing is simple, safe, low-cost and noninvasive. Comprehensive analysis and identification of the proteomic content in human whole and ductal saliva will not only contribute to the understanding of oral health and disease pathogenesis, but also form a foundation for the discovery of saliva protein biomarkers for human disease detection. In this article, we have summarized the proteomic technologies for comprehensive identification of proteins in human whole and ductal saliva. We have also discussed potential quantitative proteomic approaches to the discovery of saliva protein biomarkers for human oral and systemic diseases. With the fast development of mass spectrometry and proteomic technologies, we are enthusiastic that saliva protein biomarkers will be developed for clinical diagnosis and prognosis of human diseases in the future.     

Proteomic analysis at the bedside: early detection of cancer

Proteomic technologies promise to accelerate rapidly a new era in molecular medicine, especially in the detection and discovery of disease-related biomarkers. These technologies have no bigger impact than in the field of human cancer research. Beyond lifestyle-associated prevention strategies, early detection of cancer has the most profound impact on the ultimate course of the disease: the earlier the cancer is detected, the better the prognosis. Today, new proteomic technologies are being used to discover new diagnostic and prognostic biomarkers for the early detection and treatment of cancer that will have important implications at the bedside.     

Antibody Engineering & Therapeutics 2015: The Antibody Society's annual meeting December 7–10, 2015, San Diego,CA

Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society, will be held in San Diego, CA in early December 2015. In this meeting preview, the chairs provide their thoughts on the importance of their session topics, which include antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, overcoming resistance to clinical immunotherapy, and building comprehensive IGVH-gene repertoires through discovering, confirming and cataloging new germline IGVH genes. The Antibody Society's special session will focus on “Antibodies to watch” in 2016, which are a subset of the nearly 50 antibodies currently in Phase 3 clinical studies. Featuring over 100 speakers in total, the meeting will commence with keynote presentations by Erica Ollmann Saphire (The Scripps Research Institute), Wayne A. Marasco (Dana-Farber Cancer Institute/Harvard Medical School), Joe W. Gray (Oregon Health & Science University), and Anna M. Wu (University of California Los Angeles), and it will conclude with workshops on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries and on computational antibody design.     

美国国家癌症研究所(National Cancer Institute)--美国癌症研究和资助的主要机构

美国国家癌症研究所(National Cancer Institute,NCI)成立于1937年,是国立卫生研究院(National Institutes of Health,NIH)历史最为悠久的研究所,也是美国癌症研究和资助的主要机构。通过立法及增加对癌症研究的投入,NCI在癌症研究领域取得一些成绩,使肺癌、结直肠癌、乳腺癌及前列腺癌的死亡率持续下降,另在胰腺癌、卵巢癌、白血病和甲状腺癌等肿瘤的诊断和治疗方面也取得了巨大成就。新近NCI制定了到20l5年的奋斗目标：“消除痛苦、减少死亡”,并将主要策略由“寻找进而破坏(seekanddestory)”转为“锁定并且控制(target and control)”。为了实现上述目标,NCI提出必须加强基础研究,以利癌症的早期发现(discovery);以此为基础,将实验室的研究结果尽快用于临床,促进各种治疗措施的发展(development);加强癌症防治的公共卫生宣传,以利于健康资讯的发布(delivery)。本文将简述NCI的历史沿革、主要目标、组织结构、资金预算以及所取得的成就。     

Antibody Engineering & Therapeutics 2015: The Antibody Society's annual meeting December 7–10, 2015, San Diego,CA

Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society, will be held in San Diego, CA in early December 2015. In this meeting preview, the chairs provide their thoughts on the importance of their session topics, which include antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, overcoming resistance to clinical immunotherapy, and building comprehensive IGVH-gene repertoires through discovering, confirming and cataloging new germline IGVH genes. The Antibody Society''s special session will focus on “Antibodies to watch” in 2016, which are a subset of the nearly 50 antibodies currently in Phase 3 clinical studies. Featuring over 100 speakers in total, the meeting will commence with keynote presentations by Erica Ollmann Saphire (The Scripps Research Institute), Wayne A. Marasco (Dana-Farber Cancer Institute/Harvard Medical School), Joe W. Gray (Oregon Health & Science University), and Anna M. Wu (University of California Los Angeles), and it will conclude with workshops on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries and on computational antibody design.     

Proteomic profiling of pancreatic cancer for biomarker discovery

Pancreatic cancer is a uniformly lethal disease that is difficult to diagnose at early stage and even more difficult to cure. In recent years, there has been a substantial interest in applying proteomics technologies to identify protein biomarkers for early detection of cancer. Quantitative proteomic profiling of body fluids, tissues, or other biological samples to identify differentially expressed proteins represents a very promising approach for improving the outcome of this disease. Proteins associated with pancreatic cancer identified through proteomic profiling technologies could be useful as biomarkers for the early diagnosis, therapeutic targets, and disease response markers. In this article, we discuss recent progress and challenges for applying quantitative proteomics technologies for biomarker discovery in pancreatic cancer.