Special Issue "Biomarkers: Oncology Studies"

Guest Editor
Dr. Sonia Pearson-White
Scientific Program Manager, The Biomarkers Consortium Foundation for the National Institutes of Health, F9650 Rockville Pike, Bethesda, MD 20814, USA
E-Mail:
Interests: molecular genetics; biomarkers; oncology; TGF-beta signaling oncogene/proto-oncogene; stem cells

Dear Colleagues,

The 2004 FDA Critical Path Initiative challenged the pharmaceutical industry to reduce the time (12-15 years) and expense (~$1-2 billion) to bring an oncology drug to market. Biomarkers are seen as key to reducing the time and expense for this. There are thousands of cancer-related biomarker references in the literature, but only a handful of oncology biomarkers have been validated for clinical use. We are interested in papers covering all aspects of biomarker discovery, validation, and qualification in any area of oncology (see cancer list at http://www.mdpi.com/journal/cancers/about). Biomarkers can be circulating molecules or cells, pharmacogenomics, GWAS, or imaging. Biomarker measurements can include techniques such as microarray analyses or signature combinations from microarrays (e.g. Mammaprint(tm)), new assays for measuring known biomarkers such as HER2 or ER, reverse phase protein microarray (RPMA), circulating tumor cells, and imaging science studies (e.g. FDG-PET, DCE-MRI, DW-MRI, MR spectroscopy). Of particular interest are biomarkers based on fundamental understanding of cancer biology, or that add to that understanding.

Dr. Sonia Pearson-White
Guest Editor

Related Special Issues in other Journals

Biomarkers: Environmental Research and Public Health in IJERPH

Submission Information

All manuscripts should be submitted to cancers@mdpi.org with a copy to the Guest Editor. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.

For the first two issues, to be published in 2009 and 2010, the Article Processing Charges (APC) will be waived for well-prepared manuscripts. English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Type of Paper: Review
Title: Inflammatory Genetic Markers of Prostate Cancer RiskArticle
Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer
Author: Anne-Marie Mes-Masson Cordially
Affiliation Centre de recherche CHUM/ICM, 1560, rue Sherbrooke est, Montréal, Québec, Canada, H2L 4M1; E-Mail: Anne-Marie.Mes-Masson@umontreal.ca
Abstract: Epithelial ovarian cancer is a leading cause of cancer-related death in women and represents the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. Consequently, the survival rate of patients is extremely low. Up to now, there are no reliable clinical factors that can properly stratify patients who would be best suited for aggressive first line chemotherapy. Clinical parameters such as disease stage, tumor grade and residual disease are helpful in the management of patients after their initial surgery to establish the first line of treatment, but are not efficient enough. Accordingly, reliable markers independent and complementary to clinical parameters are needed for a better management of these patients. For several years efforts to identify prognostic factors have focused on molecular markers. A large number of molecular markers have been investigated to date. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in tissue of ovarian cancer patients, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer.

Authors: Elizabeth A. Tindall, Desiree C. Petersen and Vanessa M. Hayes
Affiliation: Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia; E-Mail: vhayes@ccia.unsw.edu.au
Abstract: Prostate cancer is the most common male cancer in Western society with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools are either invasive or subjective to external stimuli. Substantial histological, epidemiological and molecular genetic evidence exists that inflammation is important in prostate cancer pathogenesis. In this review we summarize the current status of inflammatory genetic markers influencing susceptibility to prostate cancer. The focus will be on inflammatory cytokines regulating T-helper cell and chemokine homeostasis, together with the Toll-like receptors as key players in the host innate immune system.

Type of Paper: Review
Title: Cancer Biomarkers: Are We Ready for the Prime Time?
Author: Mukesh Verma
Affiliation: Epidemiology and Genetics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, 6130 Executive Blvd., Room 5100, Bethesda, MD 20892-7324, Rockville, MD 20852, USA; E-Mail: vermam@mail.nih.gov
Abstract: A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In cancer, a biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker might be either a molecule secreted by tumor itself, or it can be a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used to for cancer diagnosis, prognosis and epidemiology. Few biomarkers have high sensitivity and specificity of detection and these markers can be assayed in non-invasively collected biofluids. However, we may not be ready for the prime time due to challenges in the field of clinical validation of biomarkers for early detection, diagnosis and monitoring of disease progression to improve long-term survival of patients.

Type of Paper: Review
Title: New Molecular and Biological Biomarkers from Tumor Tissues or a Circulating Tumor/ Tumor-Related Cells and CDC/ADCC
Author: Kiyohiko Hatake
Affiliation: Division of Medical Oncology, Hematology, Ambulatory therapy center, Newer drug development center, Division of Clinical Chemotherapy, Cancer Chemotherapy Center, Olympus Bio-imaging Laboratory, Cancer Institute Hospital, 3-10-6, Ariake, Koto-ku, 135-8550 Tokyo, Japan; E-Mail: khatake@jfcr.or.jp
Abstract: Molecular biomarkers such as K-ras, B-raf, smad4, ALK and biological markers such as circulating tumor cells, circulating endothelial progenitors and CDC/ADCC susceptibility can predict the response or resistance to molecular targeting drugs. K-ras is a topical key gene to determine the indication of anti-EGFR antibody-containing treatment for colorectal cancer, and ALK is a key molecule to determine anti-ALK inhibitors. In the downstream of EGFR signal transduction, B-raf or PI3KA is important determinant. CDC/ADCC is a powerful tool for determination of the response to antibody for lymphoma, breast cancer and colorectal cancer. We introduce the bio-imaging system for minute sample analysis for biomarkers.

Type of Paper: Review
Title: Identification of the Receptor for Alpha-fetoprotein and Its derived Peptides: Review Of A Potential New Cancer Biomarker
Author: Gerald J. Mizejewski
Affiliation: Fetal Defect Markers Laboratory Wadsworth Research Center, Albany, New York 12201, USA; E-Mail: mizejew@wadsworth.org
Abstract: The identification of a putative receptor for Alpha-fetoprotein (AFP) has long been sought in the biomedical literature. The uptake of AFP by rat tumor cells in 1983 spurred a series of published reports that not only confirmed these observations, but also extended them to include multiple tumor types in rats, mice, and humans.The following year, French investigators partially characterized the binding properties of the AFP receptor but were unable to purify the receptor.It was not until 1991-1992 that an AFP receptor was isolated (not purified) and partially characterized from human monocytes and breast cancer cells. By 1993, a monoclonal antibody was produced against the breast cancer version of the AFP receptor with claims that the receptor was a widespread (universal) oncofetal antigen biomarker for cancer. However, the receptor has yet to this day been cloned and/or purified due to its complex multimeric composition. The present report will review the literature of the AFP receptor including cellular uptake of AFP, free and bound molecular forms, and characterization of the reported cell surface receptors. Evidence derived from computer modeling, proteolytic degradation patterns, and proteonomic analysis will be presented as tenative identification of a gene family that fits most, if not all, the criteria required for the AFP receptor.

Type of Paper: Review
Title: Molecular Mechanisms of Mouse Skin Tumor Promotion
Authors: Joyce E. Rundhaug and Susan M. Fischer
Affiliation: U. TX. M.D. Anderson Cancer Center, Science Park - Research Division, P.O. Box 389, Smithville, TX 78957, USA; E-Mail: jrundhaug@mdanderson.org
Abstract: Multiple molecular mechanisms are involved in the promotion of skin carcinogenesis. Induction of sustained proliferation and epidermal hyperplasia by direct activation of mitotic signaling pathways or indirectly in response to chronic wounding and/or inflammation is necessary to allow clonal expansion of initiated cells with DNA mutations to form skin tumors. The mitotic pathways include activation of epidermal growth factor receptor and Ras/Raf/mitogen-activated protein kinase signaling. Chronic inflammation results in inflammatory cell secretion of growth factors and cytokines such as tumor necrosis factor-alpha and interleukins, as well as production of reactive oxygen species, all of which can stimulate proliferation. Persistent activation of these pathways leads to tumor promotion.

Type of Paper: Review
Title: Biomarkers for Early Detection of Malignant Mesothelioma: Diagnostic and Therapeutic Application
Author: Marco Tomasetti
Affiliation: Dept Mol Pathol & Innov Therapies, Polytechnic University of Marche, Ancona, Italy; E-Mail: m.tomasetti@univpm.it
Abstract: Malignant Mesothelioma (MM) is a rare and aggressive tumour of serosal cavities linked to asbestos exposure. Improved detection methods for diagnosis of this type of neoplastic disease are essential for an early and reliable detection and treatment. Thus, focus has been on finding tumour markers used for non-invasive detection of MM. Recently, some blood biomarkers have been described as a potential indicator of early and advanced MM cancers. A combination of biomarkers could be used to stratify the risk of mesothelioma in asbestos-exposed populations. The epigenetic changes during the cell transformation and the altered gene expression provide fingerprints that may serve as molecular biomarkers for tumour diagnosis, classification, prognosis and prediction of therapeutic responses.

Type of Paper: Review
Title: Biomarkers for the Optimization of Anti-Angiogenic Therapies
Author: Francesco Bertolini
Affiliation: Hematology-Oncology Unit, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy; E-Mail: francesco.bertolini@ieo.it
Abstract: The dependence of tumour growth and metastasis on blood vessels makes tumour angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and/or destroy existing tumour vessels, including direct targeting of endothelial cells, and indirect targeting by inhibiting the release of proangiogenic growth factors by cancer or stromal cells. By viewing the process of angiogenesis as an 'organizing principle' in biology, one can gain insights into the molecular and cellular mechanisms of seemingly unrelated phenomena. This has important consequences for the clinical use of angiogenesis inhibitors and for drug discovery, not only for optimizing the treatment of cancer, but possibly also for developing therapeutic approaches for various diseases.
Keywords: angiogenesis; anti-angiogenic therapies; oncology; cancer

Type of Paper: Review
Title: The emerging role of podoplanin in tumor invasion and metastasis
Author: Miguel Quintanilla
Affiliation: Instituto de Investigaciones Biomédicas Alberto Sols , CSIC-UAM, Arturo Duperier 4, 28029-Madrid, Spain; E-Mail: mquintanilla@iib.uam.es
Abstract: Podoplanin (also called PA2.26 antigen, Aggrus and T1a) is a small membrane mucin normally expressed in the lymphatic but not blood vessel endothelium which is widely used as an immunohistochemical marker to study the organization of the lymphatic vasculature and the presence of lymphangiogenesis in tumors. Podoplanin is also expressed in a variety of tissues such as mesothelia, osteoblasts, osteocytes, several epithelia and certain types of neurons. Studies with podoplanin-deficient mice have revealed an important role of the glycoprotein in the morphogenesis of the lung, formation of the lymphatic vasculature and cardiac development. Nevertheless, the biological role of podoplanin in normal tissues remains to be elucidated. Podoplanin expression is upregulated in a variety of cancers including testicular germ cell tumors, malignant mesotheliomas, central nervous system tumors, and squamous cell carcinomas (SCCs) of the skin, oral cavity, larynx, lung, cervix and oesophagus. Podoplanin is also present in activated stromal fibroblasts of carcinomas (although the clinical significance of this finding remains controversial) and has recently been identified as a candidate cancer stem cell marker in SCCs. Several reports support an important role of podoplanin in malignant progression. First, the podoplanin ectodomain contains a highly conserved motif (PLAG domain) which is critical for its platelet aggregation-inducing activity. Through the PLAG domain podoplanin expressed on the surface of tumor cells interacts with its C-type lectin-like receptor-2 protein on platelets facilitating tumor-platelet aggregate formation and pulmonary metastasis. Second, it has been reported that podoplanin is expressed at the invading front of the tumors. In a model of pancreatic /b/-cell carcinogenesis, podoplanin was able to stimulate collective tumor cell migration/invasion bypassing down-regulation of E-cadherin expression and epithelial-mesenchymal transition (EMT). Third, we have shown that the cytoplasmic domain of podoplanin binds ezrin/moesin members of the ERM (ezrin, radixin, moesin) protein family linking the glycoprotein to the actin cytoskeleton. This interaction is crucial for podoplanin-mediated activation of the small GTPase RhoA and for promotion of cell scattering and EMT. Podoplanin-induced EMT was shown to be associated with increased tumor cell migration/invasion and the acquisition of the ability to metastasize lymph nodes. Gene expression profiling studies by cDNA microarrays during podoplanin-mediated cell scattering and EMT reveal an important role of this glycoprotein in cytoskeletal and extracellular matrix remodelling.

Type of Paper: Review
Title: Midkine: a novel prognostic biomarker for cancer
Author: Yukio Ando
Affiliation: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan; E-Mail: andoy709@kumamoto-u.ac.jp
Abstract: Development of sensitive, specific, and non-invasive tumor markers, especially, in blood, is urgently needed to have a prognostic biomarker at the early stage of various types of tumors. Midkine (MK), a plasma secreted protein, was initially identified in embryonal carcinoma cells at early stages of retinoic acid-induced differentiation. Multiple studies have reported that MK plays important roles in tumor progression, and is expressed highly in various malignant tumors. Because increased blood MK levels also have been reported in patients with various tumors, serum MK concentrations may have the potential to become a very useful tumor marker. Here, we review and discuss the possibility and usefulness of MK as a novel tumor marker.

Type of Paper: Review
Title: Development of Biomarkers for Glioma
Authors: Jing Zhang and Biaoyang Lin
Affiliation: Dept. of Urology, University of Washington, Seattle, WA, USA; E-Mail: bylin@u.washington.edu
Abstract: Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary intrinsic brain tumor in humans. Because of its high aggressiveness and poor prognosis, survival of GBM patients is very low, even with aggressive surgical, radio- and chemo- therapies. Biomarkers for early diagnosis, for predicting chemo- and radio-therapy response, as well as for tumor imaging and in monitoring disease progression are all needed. Here, we review recent progress in biomarker discoveries using advanced genomics, proteomics and nanotechnologies.

Type of Paper: Review
Title: Serum Biomarkers for Detection of Gynecologic Cancers
Authors: Yutaka Ueda and Takayuki Enomoto
Affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; E-Mail: ZVF03563@nifty.ne.jp
Abstract: Ovarian, endometrial and cervical cancers are the three most common malignancies of the female reproductive organs. In 2005, around 20000, 37000 and 12000 women in the U.S.A were diagnosed as an ovarian, an endometrial and a cervical cancer, respectively. CA125, which is the most reliable serum marker for ovarian cancers, is elevated in only 50-60% of early stage ovarian cancers. For endometrial cancers, there are no established serum markers. SCC, which is the best studied serum marker for squamous cell carcinomas, is elevated in only 30-60% of early stage cervical squamous cell carcinomas. Recent proteomics-based analyses show great promise of discovery of sensitive and specific biomarkers. In this review we discuss the serum tumor markers that are currently utilized with limited value and the novel biomarkers for detection of gynecologic cancers.

Type of Paper: Review
Title: Platelet Proteome and Tumor Dormancy: Platelets Content as Biomarkers for Early Tumor Stages
Authors: Nava Almog and Giannoula Klement
Affiliation: Center of Cancer Systems Biology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA; E-Mail: Nava.Almog@tufts.edu
Abstract: Dormant microscopic tumors are highly prevalent in normal population as well as in cancer patients and are undetectable by most currently used imaging technologies. Dormant tumors are defined as microscopic and asymptomatic cancerous lesions that remain occult for prolonged periods of time. We have recently reported that the levels of angiogenesis regulatory proteins in circulating platelets change in mice bearing human tumor xenografts and that even a microscopic tumor can affect the platelet concentrations of such proteins. The “platelet proteome”, therefore, may be used to detect tumor establishment or recurrence before the tumor becomes symptomatic.

Type of Paper: Review
Title: Biomarkers for Incoming Drugs in Human Gliomas
Authors: Ana Custodio¹, Inmaculada Ibañez de Caceres^1,2, Javier de Castro¹, Rosario Perona² and Cristobal Belda-Iniesta¹
Affiliations: ¹ Translational Oncology and Experimental Therapeutics Unit CSIC/UAM at Medical Oncology Division, University Hospital La Paz, Paseo de la Castellana, 261, Madrid, Spain; E-Mail: cbelda.hulp@salud.madrid.org
² Translational Oncology and Experimental Therapeutics Unit CSIC/UAM at Biomedical Research Institute “Alberto Sols”, c/Arturo Duperier 9, Madrid, Spain
Abstract: Gliomas are the most prevalent type of primary brain tumor in adults and the prognosis of patients remains poor. In addition, clinical heterogeneity is a fact and patients with a same histological diagnosis may have disparate therapeutic outcomes. So, neuro-oncologists need biomarkers to predict tumour behaviour that allow clinicians to delineate an appropriate and personalized approach for individual patients. An increased understanding of the molecular pathways involved in progression of gliomas has led to the isolation of potential diagnostic, prognostic, and predictive biomarkers, some bearing clinical implications for targeted therapy. Nowadays, chromosome 1p/19q codeletions in oligodendrogliomas, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation or epidermal growth factor receptor (EGFR)-PI3 kinase pathway status in glioblastomas are of clinical relevance because we can choose patients therapy according to these biomarkers. Next future, new drugs with highly complex mechanisms of action will arrive for many patients. In cooperation with this therapeutic arsenal, molecular profiling studies continuously supply information about biological relevance of potential biomarkers of likely clinical interest, including signaling pathways involved in sustained proliferation, disturbances on cell cycle control, genomic instability, promotion of cell migration/invasion and resistance to apoptosis. Furthermore, several proangiogenic factors, such as vascular endothelial growth factor (VEGF) , hypoxia inducible factor-1 alpha (HIF-1alpha), angiopoietin-1/ 2, platelet derived growth factor BB (PDGF-BB) or scatter factor/hepatocyte growth factor (SF/HGF), are emerging as promising determinants of prognosis. Neuro- oncologists need to be aware about all the potential correlations among new drugs and new biomarkers that will be here in next years. So, this review summarizes relevant biomarkers for future, incoming drugs that will shift neuro-oncology to a new age of clinical results.

Title: Small-Cell Lung Cancer-Associated Autoantibodies as Biomarkers for SCLC Detection
Authors: Meleeneh Kazarian and Ite A. Laird-Offringa
Affiliation: Departments of Surgery and of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California/Norris Cancer Center, 1441 Eastlake Ave. NOR6420, Los Angeles, CA 90089-9176, USA; E-Mail: ilaird@usc.edu(I.A.L.O.)
Abstract: Small-cell lung cancer (SCLC) is the most aggressive lung cancer subtype and lacks effective early detection methods. In this review, the diagnostic value, the potential protective role, and the therapeutic possibilities of SCLC-associated autoantibodies will be discussed. There are a number of rare paraneoplastic neurologic autoimmune diseases that are strongly associated with SCLC. Most patients with these diseases have underlying SCLC and harbor high titers of antibodies against neuronal proteins. Abnormal expression of these neuronal proteins in SCLC tumors is thought to result in the generation of autoantibodies that may cross-react with the nervous system, possibly triggering an autoimmune response. Here we discuss the proposed roles these autoantibodies play in the pathogenesis of SCLC-associated paraneoplastic neurologic disorders and how these autoantibodies may be employed to study the development of SCLC-associated autoimmunity, the cause of which is currently unknown. We evaluate emerging technologies to study and detect these autoantibodies, including SCLC mouse models, multiplexing strategies, and proteomics. Several studies indicate that the presence of these autoantibodies is associated with indolent tumor growth and prolonged survival. Thus, we will discuss the clinical implications of these autoantibodies as well as their potential clinical applications, for example tumor associated antigen (TAA)/antibody panels, immunotherapy, and early detection of SCLC.
Keywords: autoantigen; onconeural; paraneoplastic; autoimmunity; mouse model; tumor-associated antigen

Type of Paper: Review
Title: Innovative Biomarker Development Strategies
Authors: Andrew V. Biankin, Susan M. Henshall and Robert L. Sutherland
Affiliation: Cancer Research Program, Garvan Institute of Medical Research, Sydney NSW, Australia; E-Mail: a.biankin@garvan.org.au
Abstract: Integrating companion biomarker discovery with therapeutic development at the pre-clinical stage creates the opportunity to identify candidate biomarkers early, which would significantly facilitate both therapeutic and biomarker development by defining responsive subgroups for targeted studies. Advances in “-omic” technologies has led to large scale efforts in characterising and cataloguing the full range of aberrations in cancer. These include the International Cancer Genome Consortium, TCGA, and the AHEAD consortium, which aim to provide detailed information for large numbers of cancers for a progressively increasing range of cancer types and subtypes. The technical challenges associated with achieving these goals in many instances have required the generation of primary xenografts and cell lines. These extensively characterised model systems will provide an unprecedented resource for the discovery of biomarkers of therapeutic responsiveness for established therapies, and the identification of companion biomarkers linked with pre-clinical novel therapeutic development.

Type of Paper: Review
Title: DNA Methylation-Based Biomarkers in Breast Cancer
Authors: F. Javier Carmona ¹ and Jürgen Veeck ²
Affiliations: ¹ Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), 08907 Barcelona, Spain; E-Mail: fjcarmona@idibell.org (FJC)
² Division of Clinical Oncology, Department of Internal Medicine, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, 6202 AZ Maastricht, The Netherlands; E-Mail: juergen.veeck@rwth-aachen.de (JV)
Abstract: Breast cancer is the leading cause of cancer-related mortality among women worldwide. Despite recent drug approvals patient overall survival still remains below five years, demonstrating the need of better diagnosis and treatment strategies. The search for tumor biomarkers has a long history in cancer research, ever aiming at improvements in diagnosis, tumor classification, patient risk stratification or prediction of response to treatment. However, only few biomarkers have emerged to the application in clinical routine. Aberrant DNA methylation in gene promoters is recognized as a hallmark of human cancer. DNA methylation efficiently inactivates transcription of important regulatory genes during all stages of tumor development from malignant cell transformation to metastasis. Due to its cellular consequences similar to genetic lesions, epigenetic gene silencing has been shown to be causally involved in tumorigenesis and progression. A plethora of genes undergoing epigenetic modification have been published in virtually any tumor type, including breast cancer. Importantly, methylation of particular genes appears to be valuable in the clinical setting for they are able to indicate tumors at early stages, distinguish between patient outcomes, or predict clinical response to adjuvant treatment. It is the aim of this review to summarize the recent literature on DNA methylation biomarkers in breast cancer potentially useful in clinical oncology.

Type of Paper: Review
Title: Biomarkers for Basal-Like Breast Cancer
Authors: Jennifer R. Choo and Torsten O. Nielsen
Affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; E-Mail: torsten@interchange.ubc.ca
Abstract: Basal-like breast cancer is an aggressive form of carcinoma with a predilection for younger women, for which we lack effective targeted therapies. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast carcinomas through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal-like breast cancer biomarker research. While a number of biomarkers show promise for future clinical application, the next logical step is a comprehensive investigation of all biomarkers against a gene expression profile gold standard for breast cancer subtype assignment.

Type of Paper: Article
Title: Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer
Author: Anne-Marie Mes-Masson Cordially
Affiliation: Centre de recherche CHUM/ICM, 1560, rue Sherbrooke est, Montréal, Québec, H2L 4M1, Canada; E-Mail: Anne-Marie.Mes-Masson@umontreal.ca
Abstract: Epithelial ovarian cancer is a leading cause of cancer-related death in women and represents the most lethal gynecological malignancy. Due to its lack of symptoms, this disease is diagnosed at an advanced stage when the cancer has already spread to secondary sites. Consequently, the survival rate of patients is extremely low. Up to now, there are no reliable clinical factors that can properly stratify patients who would be best suited for aggressive first line chemotherapy. Clinical parameters such as disease stage, tumor grade and residual disease are helpful in the management of patients after their initial surgery to establish the first line of treatment, but are not efficient enough. Accordingly, reliable markers independent and complementary to clinical parameters are needed for a better management of these patients. For several years efforts to identify prognostic factors have focused on molecular markers. A large number of molecular markers have been investigated to date. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in tissue of ovarian cancer patients, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer.

Type of Paper: Review
Title: The Evolution of Biomarkers in Thyroid Cancer – From Mass Screening to a Personalized Biosignature
Authors: Raymon H. Grogan, Elliot J. Mitmaker and Orlo H. Clark
Affliation: UCSF Division of Endocrine Surgery, 1600 Divisadero St., C-347, Box 1674 San Francisco, CA 94143, USA; E-Mail: orlo.clark@ucsfmedctr.org
Abstract: Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of fifty. Yet only 5% of these patients will be diagnosed with cancer. Fine needle aspiration biopsy is the gold standard for diagnosing thyroid nodules. However, 10-15% of these biopsies are inconclusive, ultimately requiring a diagnostic thyroid lobectomy. Consequently, research in thyroid biomarkers has become an area of active interest. In the forty years since calcitonin was first described as the biomarker for medullary thyroid cancer, new biomarkers in thyroid cancer have been discovered. Advances in genomic and proteomic technologies have defined many of these novel thyroid biomarkers. The purpose of this article is to provide a comprehensive literature review of how these biomarkers have evolved from simple screening tests into a complex array of multiple markers to help predict the malignant potential and genetic signature of thyroid neoplasms.

Type of Paper: Review
Titel: The Evolution of Biomarkers in Thyroid Cancer – From Mass Screening to a Personalized Biosignature
Authors: Raymon H. Grogan, Elliot J. Mitmaker and Orlo H. Clark
Affiliation: UCSF Division of Endocrine Surgery, 1600 Divisadero St., C-347, Box 1674 San Francisco, CA 94143, USA; E-Mail: orlo.clark@ucsfmedctr.org
Abstract: Thyroid cancer is the most common malignancy of the endocrine system. The diagnosis of thyroid nodules, made by neck examination and ultrasonography, is a common event occurring in over 50% of the patient population over the age of fifty. Yet only 5% of these patients will be diagnosed with cancer. Fine needle aspiration biopsy is the gold standard for diagnosing thyroid nodules. However, 10-15% of these biopsies are inconclusive, ultimately requiring a diagnostic thyroid lobectomy. Consequently, research in thyroid biomarkers has become an area of active interest. In the forty years since calcitonin was first described as the biomarker for medullary thyroid cancer, new biomarkers in thyroid cancer have been discovered. Advances in genomic and proteomic technologies have defined many of these novel thyroid biomarkers. The purpose of this article is to provide a comprehensive literature review of how these biomarkers have evolved from simple screening tests into a complex array of multiple markers to help predict the malignant potential and genetic signature of thyroid neoplasms.

Type of Paper: Review
Title: Aberrant Crypt Foci: The Case for Inclusion as a Relevant Biomarker for Colon Cancer
Authors: Michael J. Wargovich, Vondina R. Brown, Kathleen V. Coleman and Jay Morris
Affiliation: Cancer Chemoprevention Program, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 28425 USA; E-Mail: wargovic@musc.edu
Abstract: Aberrant crypt foci (ACF) are one of the earliest histopathological manifestations of colon cancer. In this review we critically present the molecular, cellular, histopathological, and chemopreventive evidence that ACF are relevant biomarkers for colon cancer. The laboratory and clinical evidence are highly suggestive that ACF are in the pathway leading to colon cancer, but not all ACF will do so. The possible fate and outcome of ACF in the progression toward colon cancer may be dependent on a number of features that define their predictive power for the prevention or progression of cancer.

Type of Paper: Review
Title: Biomarkers of Metabolic Syndrome and Breast Cancer
Authors: Qiu-Li Zhu ¹, Wang-Hong Xu ¹ and Meng-Hua Tao ^2
1 Department of Epidemiology, School of Public Health, Fudan University, Shanghai, P.R. China; E-Mail: wanghong.xu@fudan.edu.cn
² Department of Social and Preventive Medicine, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY 14214, USA; E-Mail: mtao@buffalo.edu
Abstract: In spite of its public health importance, our understanding of the mechanisms for breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a cluster of metabolic disorders including visceral adiposity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. The MS has all been related to late-stage disease and even a poor prognosis of breast cancer through multiple interacting mechanisms. In this review, we aim to present a summary of recent advances in the understanding of the contribution of the MS to breast cancer with the emphasis on the role of biomarkers of MS in the prognosis of breast cancer.
Keywords: metabolic syndrome; breast cancer; survivorship; epidemiology

Type of Paper: Review
Title: An Overview of Biomarkers and Molecular Signatures in HCC
Authors: Seon-Hee Yim ^1,2 and Yeun-Jun Chung ^1,3
Affiliations: ¹ Integrated Research Center for Genome Polymorphism, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
² Department of Pathology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea
³ Department of Pathology, The Catholic University of Korea School of Medicine, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea; E-Mail: yejun@catholic.ac.kr
Abstract: Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Surgery is the only potentially curative option for HCC, yet recurrence rates are high, which results in a poor prognosis. The ability to predict individual prognosis would help clinicians to choose therapeutic modalities. A number of candidate molecular markers with prognostic significance have been reported through studies using whole genome screening technologies such as gene expression arrays and array CGH. These markers may enable more accurate prediction of prognosis and provide targets for potential therapeutic agents. In this review, we focus on candidate molecular markers reported in HCC and their implications.

Type of Paper: Review
Title: Development and Application of Tissue Microarrays for Biomarker Studies
Author: Erin Maresh
Affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; E-Mail: emaresh@mednet.ucla.edu
Abstract: Traditional methods for analyzing large numbers of tissue samples require significant amounts of time, plentiful costly reagents, and highly skilled technicians. The development of tissue microarrays has provided an alternative method, allowing for high-throughput screening and analysis of thousands of samples on a single slide. This has powerful implications for the identification and characterization of biomarkers involved in cancer progression and outcome. In this review, we describe methods of designing and constructing a tissue microarray, as well as techniques for quantifying and analyzing biomarker expression using a tissue microarray.