Special Issue "Biomarkers: Oncology Studies"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2010)

Special Issue Editor

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
Phone: +1 301-435-4103
Interests: molecular genetics; biomarkers; oncology; TGF-beta signaling oncogene/proto-oncogene; stem cells

Special Issue Information

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

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Published Papers (29 papers)

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Research

Jump to: Review

Open AccessArticle Responsiveness of Urinary and Plasma Alkylresorcinol Metabolites to Rye Intake in Finnish Women
Cancers 2010, 2(2), 513-522; doi:10.3390/cancers2020513
Received: 9 April 2010 / Revised: 12 April 2010 / Accepted: 12 April 2010 / Published: 14 April 2010
Cited by 8 | PDF Full-text (237 KB) | HTML Full-text | XML Full-text
Abstract
Alkylresorcinols [ARs] have been proposed for use as biomarkers of whole-grain intake. The aim here was to examine the responsiveness of AR metabolites to rye intake. Sixty women were divided into three groups according to their rye consumption. We observed significant differences [...] Read more.
Alkylresorcinols [ARs] have been proposed for use as biomarkers of whole-grain intake. The aim here was to examine the responsiveness of AR metabolites to rye intake. Sixty women were divided into three groups according to their rye consumption. We observed significant differences between groups in plasma 3-[3,5-dihydroxyphenyl]-1-propanoic acid [DHPPA] and in urinary DHPPA and 3,5-dihydroxybenzoic acid [DHBA]. In addition, these AR metabolites increased proportionally to rye fiber intake. We conclude that these ARs metabolites are accurate and useful biomarkers of rye fiber intake. Further studies are needed to confirm our results in larger and different populations. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessArticle Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study
Cancers 2010, 2(2), 420-435; doi:10.3390/cancers2020420
Received: 2 March 2010 / Revised: 26 March 2010 / Accepted: 7 April 2010 / Published: 12 April 2010
Cited by 2 | PDF Full-text (267 KB) | HTML Full-text | XML Full-text
Abstract
Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic [...] Read more.
Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic damage in the presence of g-radiation; an established risk factor for gliomas. We tested the hypothesis that HCMV infection modifies the sensitivity of cells to γ-radiation-induced genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma patients and 100 controls to measure the level of chromosome damage and cell death. We evaluated baseline, HCMV-, γ-radiation and HCMV + γ-radiation induced genetic instability with the comprehensive Cytokinesis-Blocked Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant increase in aberration frequency among cases and controls. PBLs infected with HCMV prior to challenge with γ-radiation led to a significant increase in aberrations as compared to baseline, γ-radiation and HCMV alone. With regards to apoptosis, glioma cases showed a lower percentage of induction following in vitro exposure to γ-radiation and HCMV infection as compared to controls. This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to γ-radiation-induced genetic damage possibly through an increase in chromosome damage and decrease in apoptosis. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessArticle Overexpression of Periostin and Lumican in Esophageal Squamous Cell Carcinoma
Cancers 2010, 2(1), 133-142; doi:10.3390/cancers2010133
Received: 27 January 2010 / Revised: 8 February 2010 / Accepted: 20 February 2010 / Published: 1 March 2010
Cited by 4 | PDF Full-text (337 KB) | HTML Full-text | XML Full-text
Abstract
To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared [...] Read more.
To identify biomarkers for early detection for esophageal squamous cell carcinoma (ESCC), we previously carried out a genome-wide gene expression profiling study using an oligonucleotide microarray platform. This analysis led to identification of several transcripts that were significantly upregulated in ESCC compared to the adjacent normal epithelium. In the current study, we performed immunohistochemical analyses of protein products for two candidates genes identified from the DNA microarray analysis, periostin (POSTN) and lumican (LUM), using tissue microarrays. Increased expression of both periostin and lumican was observed in 100% of 137 different ESCC samples arrayed on tissue microarrays. Increased expression of periostin and lumican was observed in carcinoma as well as in stromal cell in the large majority of cases. These findings suggest that these candidates can be investigated in the sera of ESCC patients using ELISA or multiple reaction monitoring (MRM) type assays to further explore their utility as biomarkers. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessArticle BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas
Cancers 2009, 1(1), 3-11; doi:10.3390/cancers1010003
Received: 27 September 2009 / Revised: 28 October 2009 / Accepted: 13 November 2009 / Published: 18 November 2009
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Abstract
We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In [...] Read more.
We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas. Interestingly, hypomethylation of BAGE loci was frequent (50%) in tubulo-villous and villous adenomas, these adenomas having a high probability of being transformed into colorectal cancers. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)

Review

Jump to: Research

Open AccessReview Aberrant Crypt Foci: The Case for Inclusion as a Biomarker for Colon Cancer
Cancers 2010, 2(3), 1705-1716; doi:10.3390/cancers2031705
Received: 28 August 2010 / Accepted: 14 September 2010 / Published: 16 September 2010
Cited by 5 | PDF Full-text (269 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment
Cancers 2010, 2(3), 1528-1554; doi:10.3390/cancers2031528
Received: 21 June 2010 / Revised: 12 July 2010 / Accepted: 13 July 2010 / Published: 27 July 2010
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Abstract
The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and [...] Read more.
The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview YKL-40—A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer Patients?
Cancers 2010, 2(3), 1453-1491; doi:10.3390/cancers2031453
Received: 13 May 2010 / Revised: 1 July 2010 / Accepted: 9 July 2010 / Published: 12 July 2010
Cited by 13 | PDF Full-text (649 KB) | HTML Full-text | XML Full-text
Abstract
YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 [...] Read more.
YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet sufficient data to support determination of plasma YKL-40 outside research projects as a biomarker for screening of gastrointestinal cancer and determination of treatment response and poor prognosis before or during treatment and follow-up. Plasma YKL-40 is also elevated in patients with other diseases than cancer, e.g., severe infections, cardiovascular disease, diabetes, chronic obstructive lung disease, asthma, liver fibrosis and rheumatoid arthritis. Co-morbidity should therefore always be considered in patients with cancer, since other sources than cancer cells can increase plasma YKL-40 levels. Future focused translational research projects combining basic and clinical research are needed in a joint effort to answer questions of the complex function and regulation of YKL-40 and the question if plasma YKL-40 is a clinical useful biomarker in patients with cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Models of Hepatocellular Carcinoma and Biomarker Strategy
Cancers 2010, 2(3), 1441-1452; doi:10.3390/cancers2031441
Received: 3 June 2010 / Revised: 2 July 2010 / Accepted: 6 July 2010 / Published: 7 July 2010
Cited by 6 | PDF Full-text (303 KB) | HTML Full-text | XML Full-text
Abstract
The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including [...] Read more.
The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview PCA3 and TMPRSS2-ERG: Promising Biomarkers in Prostate Cancer Diagnosis
Cancers 2010, 2(3), 1432-1440; doi:10.3390/cancers2031432
Received: 17 May 2010 / Revised: 24 June 2010 / Accepted: 5 July 2010 / Published: 6 July 2010
Cited by 4 | PDF Full-text (182 KB) | HTML Full-text | XML Full-text
Abstract
The search for the biomarkers to precisely and non-invasively characterize the biology of prostate cancer (PCa) is the focus of many laboratories across the world. Although prostate-specific antigen (PSA) remains the standard diagnostic tool for PCa, its low specificity leads to unnecessary [...] Read more.
The search for the biomarkers to precisely and non-invasively characterize the biology of prostate cancer (PCa) is the focus of many laboratories across the world. Although prostate-specific antigen (PSA) remains the standard diagnostic tool for PCa, its low specificity leads to unnecessary biopsies in a substantial number of patients. More importantly, with the current status of knowledge, it is very difficult to early identify individuals with a life-threatening disease who require an immediate treatment. The significant advances in genetics and biotechnology in recent years has led to the discovery of new molecular markers including PCA3 and the TMPRSS2:ERG genomic fusion. Both PCA3 and TMPRSS2:ERG, compared to PSA, show an increased specificity in PCa detection. However, the quest for a single PCa marker that can fully satisfy urologists and their patients is still ongoing. The aim of this review is to present the recent findings on PCA3 and TMPRSS2:ERG and to describe their clinical implications and performance. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Alterations of MicroRNAs in Solid Cancers and Their Prognostic Value
Cancers 2010, 2(2), 1328-1353; doi:10.3390/cancers2021328
Received: 23 April 2010 / Revised: 2 June 2010 / Accepted: 10 June 2010 / Published: 14 June 2010
Cited by 13 | PDF Full-text (269 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with [...] Read more.
MicroRNAs (miRNAs) are evolutionarily conserved, naturally abundant, small, regulatory non-coding RNAs that inhibit gene expression at the post-transcriptional level in a sequence-specific manner. Each miRNA represses the protein expression of several coding genes in a manner proportional to the sequence complementarity with the target transcripts. MicroRNAs play key regulatory roles in organismal development and homeostasis. They control fundamental biological processes, such as stem-cell regulation and cellular metabolism, proliferation, differentiation, stress resistance, and apoptosis. Differential miRNA expression is found in malignant tumors in comparison to normal tissue counterparts. This indicates that miRNA deregulation contributes to the initiation and progression of cancer. Currently, miRNA expression signatures are being rigorously investigated in various tumor types, with the aim of developing novel, efficient biomarkers that can improve clinical management of cancer patients. This review discusses deregulated miRNAs in solid tumors, and focuses on their emerging prognostic potential. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging
Cancers 2010, 2(2), 1251-1287; doi:10.3390/cancers2021251
Received: 27 May 2010 / Revised: 31 May 2010 / Accepted: 2 June 2010 / Published: 11 June 2010
Cited by 36 | PDF Full-text (5241 KB) | HTML Full-text | XML Full-text
Abstract
Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular [...] Read more.
Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Inflammatory Genetic Markers of Prostate Cancer Risk
Cancers 2010, 2(2), 1198-1220; doi:10.3390/cancers2021198
Received: 6 May 2010 / Revised: 24 May 2010 / Accepted: 1 June 2010 / Published: 8 June 2010
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Abstract
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack [...] Read more.
Prostate cancer is the most common cancer in Western society males, with incidence rates predicted to rise with global aging. Etiology of prostate cancer is however poorly understood, while current diagnostic tools can be invasive (digital rectal exam or biopsy) and/or lack specificity for the disease (prostate-specific antigen (PSA) testing). Substantial histological, epidemiological and molecular genetic evidence indicates 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. Although association studies indicating a genetic basis for prostate cancer are presently limited mainly due to lack of replication, larger and more ethnically and clinically defined study populations may help elucidate the true contribution of inflammatory gene variants to prostate cancer risk. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Significance of Micrometastases: Circulating Tumor Cells and Disseminated Tumor Cells in Early Breast Cancer
Cancers 2010, 2(2), 1221-1235; doi:10.3390/cancers2021221
Received: 10 May 2010 / Revised: 26 May 2010 / Accepted: 4 June 2010 / Published: 8 June 2010
Cited by 3 | PDF Full-text (193 KB) | HTML Full-text | XML Full-text
Abstract
Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment [...] Read more.
Adjuvant systemic therapy targets minimal residual disease. Our current clinical approach in the adjuvant setting is to presume, rather than confirm, the presence of minimal residual disease. Based on assessment of the primary tumor, we estimate an individual’s recurrence risk. Subsequent treatment decisions are based on characteristics of the primary tumor, with the presumption of consistent biology and treatment sensitivity between micrometastases and the primary lesion. An alternative approach is to identify micrometastatic disease. Detection of disseminated tumor cells (DTC) in the bone marrow and circulating tumor cells (CTC) from peripheral blood collection may offer quantification and biocharacterization of residual disease. This paper will review the prognostic and predictive potential of micrometastatic disease in early breast cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Markers for Detection of Prostate Cancer
Cancers 2010, 2(2), 1125-1154; doi:10.3390/cancers2021125
Received: 22 March 2010 / Revised: 2 June 2010 / Accepted: 3 June 2010 / Published: 4 June 2010
Cited by 14 | PDF Full-text (958 KB) | HTML Full-text | XML Full-text
Abstract
Early detection of prostate cancer is problematic, not just because of uncertainly whether a diagnosis will benefit an individual patient, but also as a result of the imprecise and invasive nature of establishing a diagnosis by biopsy. Despite its low sensitivity and [...] Read more.
Early detection of prostate cancer is problematic, not just because of uncertainly whether a diagnosis will benefit an individual patient, but also as a result of the imprecise and invasive nature of establishing a diagnosis by biopsy. Despite its low sensitivity and specificity for identifying patients harbouring prostate cancer, serum prostate specific antigen (PSA) has become established as the most reliable and widely-used diagnostic marker for this condition. In its wake, many other markers have been described and evaluated. This review focuses on the supporting evidence for the most prominent of these for detection and also for predicting outcome in prostate cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Reinventing Diagnostics for Personalized Therapy in Oncology
Cancers 2010, 2(2), 1066-1091; doi:10.3390/cancers2021066
Received: 6 April 2010 / Revised: 15 May 2010 / Accepted: 28 May 2010 / Published: 2 June 2010
PDF Full-text (252 KB) | HTML Full-text | XML Full-text
Abstract
Human cancers are still diagnosed and classified using the light microscope. The criteria are based upon morphologic observations by pathologists and tend to be subject to interobserver variation. In preoperative biopsies of non-small cell lung cancers, the diagnostic concordance, even amongst experienced [...] Read more.
Human cancers are still diagnosed and classified using the light microscope. The criteria are based upon morphologic observations by pathologists and tend to be subject to interobserver variation. In preoperative biopsies of non-small cell lung cancers, the diagnostic concordance, even amongst experienced pulmonary pathologists, is no better than a coin-toss. Only 25% of cancer patients, on average, benefit from therapy as most therapies do not account for individual factors that influence response or outcome. Unsuccessful first line therapy costs Canada CAN$1.2 billion for the top 14 cancer types, and this extrapolates to $90 billion globally. The availability of accurate drug selection for personalized therapy could better allocate these precious resources to the right therapies. This wasteful situation is beginning to change with the completion of the human genome sequencing project and with the increasing availability of targeted therapies. Both factors are giving rise to attempts to correlate tumor characteristics and response to specific adjuvant and neoadjuvant therapies. Static cancer classification and grading systems need to be replaced by functional classification systems that not only account for intra- and inter- tumor heterogeneity, but which also allow for the selection of the correct chemotherapeutic compounds for the individual patient. In this review, the examples of lung and breast cancer are used to illustrate the issues to be addressed in the coming years, as well as the emerging technologies that have great promise in enabling personalized therapy. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Blood-Based Biomarkers for the Optimization of Anti-Angiogenic Therapies
Cancers 2010, 2(2), 1027-1039; doi:10.3390/cancers2021027
Received: 29 March 2010 / Revised: 11 May 2010 / Accepted: 27 May 2010 / Published: 28 May 2010
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Abstract
The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect [...] Read more.
The dependence of tumor growth and metastasis on blood vessels makes tumor angiogenesis a rational target for therapy. Strategies have been pursued to inhibit neovascularization and to destroy existing tumor vessels, or both. These include direct targeting of endothelial cells, and indirect targeting by inhibiting the release of proangiogenic growth factors by cancer or stromal cells. Many patients benefit from antiangiogenic therapies; thus, development of noninvasive biomarkers of disease response and relapse is a crucial objective to aid in their management. A number of non-invasive tools are described with their potential benefits and limitations. We review currently available candidate biomarkers of anti-angiogenic agent effect. Including these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, and prediction of individual response. 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 other diseases. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Biomarkers for Basal-like Breast Cancer
Cancers 2010, 2(2), 1040-1065; doi:10.3390/cancers2021040
Received: 19 March 2010 / Revised: 11 May 2010 / Accepted: 19 May 2010 / Published: 28 May 2010
Cited by 15 | PDF Full-text (484 KB) | HTML Full-text | XML Full-text
Abstract
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification [...] Read more.
Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer 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. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Predictive and Prognostic Protein Biomarkers in Epithelial Ovarian Cancer: Recommendation for Future Studies
Cancers 2010, 2(2), 913-954; doi:10.3390/cancers2020913
Received: 8 March 2010 / Revised: 19 April 2010 / Accepted: 13 May 2010 / Published: 26 May 2010
Cited by 13 | PDF Full-text (500 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Epithelial ovarian cancer is 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. While initial rates of response to first treatment is >80%, [...] Read more.
Epithelial ovarian cancer is 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. While initial rates of response to first treatment is >80%, the overall survival rate of patients is extremely low, mainly due to development of drug resistance. To date, there are no reliable clinical factors that can properly stratify patients for suitable chemotherapy strategies. Clinical parameters such as disease stage, tumor grade and residual disease, although helpful in the management of patients after their initial surgery to establish the first line of treatment, are not efficient enough. Accordingly, reliable markers that are 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, with a large number having been investigated. This review aims to present a summary of the recent advances in the identification of molecular biomarkers in ovarian cancer patient tissues, as well as an overview of the need and importance of molecular markers for personalized medicine in ovarian cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview The Evolution of Biomarkers in Thyroid Cancer—From Mass Screening to a Personalized Biosignature
Cancers 2010, 2(2), 885-912; doi:10.3390/cancers2020885
Received: 26 March 2010 / Revised: 10 May 2010 / Accepted: 19 May 2010 / Published: 20 May 2010
Cited by 10 | PDF Full-text (255 KB) | HTML Full-text | XML Full-text
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 50. Yet, only 5% [...] Read more.
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 50. 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 40 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. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Platelet Proteome and Tumor Dormancy: Can Platelets Content Serve as Predictive Biomarkers for Exit of Tumors from Dormancy?
Cancers 2010, 2(2), 842-858; doi:10.3390/cancers2020842
Received: 11 March 2010 / Revised: 30 April 2010 / Accepted: 5 May 2010 / Published: 11 May 2010
Cited by 9 | PDF Full-text (171 KB) | HTML Full-text | XML Full-text
Abstract
Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the [...] Read more.
Although tumor dormancy is highly prevalent, the underling mechanisms are still mostly unknown. It is unclear which lesions will progress and become a disseminated cancer, and which will remain dormant and asymptomatic. Yet, an improved ability to predict progression would open the possibility of timely treatment and improvement in outcomes. We have recently described the ability of platelets to selectively uptake angiogenesis regulators very early in tumor growth, and proposed their use as an early marker of malignancy. In this review we will summarize current knowledge about these processes and will discuss the possibility of using platelet content to predict presence of occult tumors. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview An Overview of Biomarkers and Molecular Signatures in HCC
Cancers 2010, 2(2), 809-823; doi:10.3390/cancers2020809
Received: 19 March 2010 / Revised: 30 April 2010 / Accepted: 7 May 2010 / Published: 7 May 2010
Cited by 10 | PDF Full-text (149 KB) | HTML Full-text | XML Full-text
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is [...] Read more.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality worldwide. Although most HCCs seem to originate from the accumulation of genetic abnormalities induced by various risk factors, underlying mechanisms of hepatocarcinogenesis remain unclear. Long-term survival of HCC patients is also poor, partly due to HCC recurrence. Although serum alpha-fetoprotein (AFP) level is a useful marker for the detection and monitoring of HCC, AFP levels may remain normal in the patients even with advanced HCC. To identify useful biomarkers for HCC, many studies have been conducted on molecular events such as genetic and epigenetic alterations, and gene expression. This review summarizes recent studies of potential molecular markers for diagnosis and monitoring metastasis or recurrence of HCC. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Biomarkers of the Metabolic Syndrome and Breast Cancer Prognosis
Cancers 2010, 2(2), 721-739; doi:10.3390/cancers2020721
Received: 23 March 2010 / Revised: 13 April 2010 / Accepted: 26 April 2010 / Published: 28 April 2010
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Abstract
In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components [...] Read more.
In spite of its public health importance, our understanding of the mechanisms of breast carcinogenesis and progress is still evolving. The metabolic syndrome (MS) is a constellation of biochemical abnormalities including visceral adiposity, hyperglycemia, hyperinsulinemia, dyslipidemia and high blood pressure. The components of the MS have all been related to late-stage disease and even to 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 the MS in the prognosis of breast cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview MicroRNAs in Head and Neck Squamous Cell Carcinoma (HNSCC) and Oral Squamous Cell Carcinoma (OSCC)
Cancers 2010, 2(2), 653-669; doi:10.3390/cancers2020653
Received: 5 March 2010 / Revised: 2 April 2010 / Accepted: 15 April 2010 / Published: 21 April 2010
Cited by 14 | PDF Full-text (85 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression [...] Read more.
MicroRNAs (miRNAs) are small, noncoding RNAs which regulate cell differentiation, proliferation, development, cell cycle, and apoptosis. Expression profiling of miRNAs has been performed and the data show that some miRNAs are upregulated or downregulated in cancer. Several studies suggest that the expression profiles of miRNAs are associated with clinical outcomes. However, the set of miRNAs with altered expressing differs depending on the type of cancer, suggesting that it is important to understand which miRNAs are related to which cancers. Therefore, this review aimed to discuss potentially crucial miRNAs in head and neck squamous cell carcinoma (HNSCC) and oral squamous cell carcinoma (OSCC). Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Galectins as Cancer Biomarkers
Cancers 2010, 2(2), 592-610; doi:10.3390/cancers2020592
Received: 2 March 2010 / Revised: 2 April 2010 / Accepted: 19 April 2010 / Published: 20 April 2010
Cited by 29 | PDF Full-text (268 KB) | HTML Full-text | XML Full-text
Abstract
Galectins are a group of proteins that bind β-galactosides through evolutionarily conserved sequence elements of the carbohydrate recognition domain (CRD). Proteins similar to galectins can be found in very primitive animals such as sponges. Each galectin has an individual carbohydrate binding preference [...] Read more.
Galectins are a group of proteins that bind β-galactosides through evolutionarily conserved sequence elements of the carbohydrate recognition domain (CRD). Proteins similar to galectins can be found in very primitive animals such as sponges. Each galectin has an individual carbohydrate binding preference and can be found in cytoplasm as well as in the nucleus. They also can be secreted through non-classical pathways and function extra-cellularly. Experimental and clinical data demonstrate a correlation between galectin expression and tumor progression and metastasis, and therefore, galectins have the potential to serve as reliable tumor markers. In this review, we describe the expression and role of galectins in different cancers and their clinical applications for diagnostic use. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Midkine: A Novel Prognostic Biomarker for Cancer
Cancers 2010, 2(2), 624-641; doi:10.3390/cancers2020624
Received: 5 March 2010 / Revised: 3 March 2010 / Accepted: 19 April 2010 / Published: 20 April 2010
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Abstract
Since diagnosis at an early stage still remains a key issue for modern oncology and is crucial for successful cancer therapy, development of sensitive, specific, and non-invasive tumor markers, especially, in serum, is urgently needed. Midkine (MK), a plasma secreted protein, was [...] Read more.
Since diagnosis at an early stage still remains a key issue for modern oncology and is crucial for successful cancer therapy, development of sensitive, specific, and non-invasive tumor markers, especially, in serum, is urgently needed. 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 highly expressed in various malignant tumors. Because increased serum MK concentrations also have been reported in patients with various tumors, serum MK 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. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
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Open AccessReview Biomarkers for Early Detection of Malignant Mesothelioma: Diagnostic and Therapeutic Application
Cancers 2010, 2(2), 523-548; doi:10.3390/cancers2020523
Received: 25 February 2010 / Revised: 1 April 2010 / Accepted: 7 April 2010 / Published: 14 April 2010
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Abstract
Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed [...] Read more.
Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Molecular Mechanisms of Mouse Skin Tumor Promotion
Cancers 2010, 2(2), 436-482; doi:10.3390/cancers2020436
Received: 4 March 2010 / Revised: 26 March 2010 / Accepted: 7 April 2010 / Published: 13 April 2010
Cited by 43 | PDF Full-text (1307 KB) | HTML Full-text | XML Full-text
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, or due to a block in terminal differentiation [...] Read more.
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, or due to a block in terminal differentiation or resistance to apoptosis 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-α 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. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Cancer Biomarkers: Are We Ready for the Prime Time?
Cancers 2010, 2(1), 190-208; doi:10.3390/cancers2010190
Received: 20 February 2010 / Revised: 2 March 2010 / Accepted: 19 March 2010 / Published: 22 March 2010
Cited by 40 | PDF Full-text (202 KB) | HTML Full-text | XML Full-text
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 [...] Read more.
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 a tumor 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 for cancer diagnosis, prognosis and epidemiology. These markers can be assayed in non-invasively collected biofluids. However, few cancer biomarkers are highly sensitive and specific for cancer detection at the present time. Consequently, biomarkers are not yet ready for routine use due to challenges in their clinical validation for early disease detection, diagnosis and monitoring to improve long-term survival of patients. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)
Open AccessReview Targeted Therapies in Epithelial Ovarian Cancer
Cancers 2010, 2(1), 88-113; doi:10.3390/cancers2010088
Received: 18 January 2010 / Revised: 2 February 2010 / Accepted: 11 February 2010 / Published: 23 February 2010
Cited by 4 | PDF Full-text (177 KB) | HTML Full-text | XML Full-text
Abstract
Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes [...] Read more.
Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer. Full article
(This article belongs to the Special Issue Biomarkers: Oncology Studies)

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