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Eleftherios P Diamandis - One of the best experts on this subject based on the ideXlab platform.
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Half-Century of Cancer Biomarkers: Lessons from the Past and Projections for the Future.
The journal of applied laboratory medicine, 2017Co-Authors: Panagiota S. Filippou, Eleftherios P DiamandisAbstract:A handful of Cancer Biomarkers are used widely in clinical practice, mainly for aiding in diagnosis and for monitoring therapy. These Biomarkers include α-fetoprotein (AFP),4 carcinoembryonic antigen (CEA), prostate-specific antigen, and the carbohydrate antigens CA125, CA19.9, and CA15.3. Other, more specialized Cancer Biomarkers are used less frequently. Molecular/genomic markers will not be discussed here. An examination of the history of these Biomarkers reveals that they were discovered in the mid-1960s and 1970s (AFP, CEA) or in the 1980s, thanks to the monoclonal antibody technology revolution. The success of these markers in clinical practice sparked interest to discover new Cancer Biomarkers that could be applied for population screening, early diagnosis, …
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Present and future of Cancer Biomarkers.
Clinical chemistry and laboratory medicine, 2014Co-Authors: Eleftherios P DiamandisAbstract:The Cancer biomarker field appears to be stagnant. Very few, if any, new Cancer Biomarkers have been introduced into clinical practice the last 20 years. The reason is that most of the newly discovered Cancer Biomarkers are inferior in terms of sensitivity and specificity to the classical Cancer Biomarkers that we currently use. The revolutionary technologies of proteomics, genomics, and other omics did not deliver on the promise to discover new and improved Cancer Biomarkers. However, more recently, the explosive growth of whole genome and exome sequencing has provided for the first time nearly complete mutational landscapes of many Cancer types, in thousands of samples. We now know that many of these mutations are only found in Cancer. It is thus possible that the mutant proteins encoded by these genes may represent the long-sought, highly specific Cancer molecules that we may envision to use as Cancer Biomarkers. I here speculate that modern mass spectrometry may have the necessary sensitivity and specificity to detect mutant proteins in various biological fluids for the purpose of diagnosis, prognosis, and disease monitoring.
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The Long Journey of Cancer Biomarkers from the Bench to the Clinic
Clinical chemistry, 2013Co-Authors: Maria P. Pavlou, Eleftherios P Diamandis, Ivan M. BlasutigAbstract:BACKGROUND: Protein Cancer Biomarkers serve multiple clinical purposes, both early and late, during disease progression. The search for new and better Biomarkers has become an integral component of contemporary Cancer research. However, the number of new Biomarkers cleared by the US Food and Drug Administration has declined substantially over the last 10 years, raising concerns regarding the efficiency of the biomarker-development pipeline. CONTENT: We describe different clinical uses of Cancer Biomarkers and their performance requirements. We also present examples of protein Cancer Biomarkers currently in clinical use and their limitations. The major barriers that candidate Biomarkers need to overcome to reach the clinic are addressed. Finally, the long and arduous journey of a protein Cancer biomarker from the bench to the clinic is outlined with an example. SUMMARY: The journey of a protein biomarker from the bench to the clinic is long and challenging. Every step needs to be meticulously planned and executed to succeed. The history of clinically useful Biomarkers suggests that at least a decade is required for the transition of a marker from the bench to the bedside. Therefore, it may be too early to expect that the new technological advances will catalyze the anticipated biomarker revolution any time soon.
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The failure of protein Cancer Biomarkers to reach the clinic: why, and what can be done to address the problem?
BMC medicine, 2012Co-Authors: Eleftherios P DiamandisAbstract:There is a plethora of published Cancer Biomarkers but the reality is that very few, if any, new circulating Cancer Biomarkers have entered the clinic in the last 30 years. I here try to explain this apparent oxymoron by classifying circulating Cancer Biomarkers into three categories: fraudulent reports (rare); true discoveries of Biomarkers, that then fail to meet the demands of the clinic; and false discoveries, which represent artifactual Biomarkers. I further provide examples of combinations of some known Cancer Biomarkers that can perform well in niche clinical applications, despite individually being not useful.
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Cancer Biomarkers: Can We Turn Recent Failures into Success?
Journal of the National Cancer Institute, 2010Co-Authors: Eleftherios P DiamandisAbstract:Disease Biomarkers are used widely in medicine. But very few Biomarkers are useful for Cancer diagnosis and monitoring. Over the past 15 years, major investments have been made to discover and validate Cancer Biomarkers. Despite such investments, no new major Cancer Biomarkers have been approved for clinical use for at least 25 years. In the last decade, many reports have described new Cancer Biomarkers that promised to revolutionize the diagnosis of Cancer and the management of Cancer patients. However, many initially promising Biomarkers have not been validated for clinical use. In this commentary, a plethora of parameters before sample analysis, during sample analysis, and after sample analysis that can complicate biomarker discovery and validation and lead to "false discovery" are discussed. Several examples of biomarker discoveries that were published in high-profile journals are also presented, as well as why they were not validated and the lessons learned from these false discoveries, so that similar mistakes can be avoided in the future.
Nashmil Emami - One of the best experts on this subject based on the ideXlab platform.
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utility of kallikrein related peptidases klks as Cancer Biomarkers
Clinical Chemistry, 2008Co-Authors: Nashmil Emami, Eleftherios P DiamandisAbstract:Background: The human kallikrein-related peptidase (KLK) family consists of 15 highly conserved serine proteases, which are encoded by the largest uninterrupted cluster of protease genes in the human genome. To date, several members of the family have been reported as potential Cancer Biomarkers. Although primarily known for their biomarker value in prostate, ovarian, and breast Cancers, more recent data suggest analogous roles of KLKs in several other Cancers, including gastrointestinal, head and neck, lung, and brain malignancies. Among the proposed KLK Cancer Biomarkers, prostate-specific antigen (also known as KLK3) is the most widely recognized member in urologic oncology. Content: Despite substantial progress in the understanding of the biomarker utility of individual KLKs, the current challenge lies in devising biomarker panels to increase the accuracy of prognosis, prediction of therapy, and diagnosis. To date, multiparametric KLK panels have been proposed for prostate, ovarian, and lung Cancers. In addition to their biomarker utility, emerging evidence has revealed a number of critical functional roles for KLKs in the pathogenesis of Cancer and their potential use as therapeutic targets. Summary: KLKs have biomarker utility in many Cancer types but individually lack sufficient specificity or sensitivity to be used in clinical practice; however, groups of KLKs and other candidate Biomarkers may offer improved performance.
Jose S Câmara - One of the best experts on this subject based on the ideXlab platform.
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investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid phase microextraction in combination with gas chromatography mass spectrometry
British Journal of Cancer, 2011Co-Authors: Catarina L Silva, M Passos, Jose S CâmaraAbstract:Investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry
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Investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry
British Journal of Cancer, 2011Co-Authors: Catarina L Silva, M Passos, Jose S CâmaraAbstract:Background: Non-invasive diagnostic strategies aimed at identifying Biomarkers of Cancer are of great interest for early Cancer detection. Urine is potentially a rich source of volatile organic metabolites (VOMs) that can be used as potential Cancer Biomarkers. Our aim was to develop a generally reliable, rapid, sensitive, and robust analytical method for screening large numbers of urine samples, resulting in a broad spectrum of native VOMs, as a tool to evaluate the potential of these metabolites in the early diagnosis of Cancer. Methods: To investigate urinary volatile metabolites as potential Cancer Biomarkers, urine samples from 33 Cancer patients (oncological group: 14 leukaemia, 12 colorectal and 7 lymphoma) and 21 healthy (control group, Cancer-free) individuals were qualitatively and quantitatively analysed. Dynamic solid-phase microextraction in headspace mode (dHS-SPME) using a carboxen-polydimethylsiloxane (CAR/PDMS) sorbent in combination with GC-qMS-based metabolomics was applied to isolate and identify the volatile metabolites. This method provides a potential non-invasive method for early Cancer diagnosis as a first approach. To fulfil this objective, three important dHS-SPME experimental parameters that influence extraction efficiency (fibre coating, extraction time and temperature of sampling) were optimised using a univariate optimisation design. The highest extraction efficiency was obtained when sampling was performed at 50°C for 60 min using samples with high ionic strengths (17% sodium chloride, w v^−1) and under agitation. Results: A total of 82 volatile metabolites belonging to distinct chemical classes were identified in the control and oncological groups. Benzene derivatives, terpenoids and phenols were the most common classes for the oncological group, whereas ketones and sulphur compounds were the main classes that were isolated from the urine headspace of healthy subjects. The results demonstrate that compound concentrations were dramatically different between Cancer patients and healthy volunteers. The positive rates of 16 patients among the 82 identified were found to be statistically different ( P
Andreas Scorilas - One of the best experts on this subject based on the ideXlab platform.
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kallikrein related peptidases klks a gene family of novel Cancer Biomarkers
Clinical Chemistry and Laboratory Medicine, 2012Co-Authors: Christos K Kontos, Andreas ScorilasAbstract:Early diagnosis of Cancer and early detection of relapse following surgery are critical for the effective treatment of the disease and for a positive clinical outcome. Identifi cation of novel diagnostic, prognostic and predictive Biomarkers will contribute utmost to clinical decision-making. The human tissue kallikrein and kallikrein-related peptidases (KLKs), encoded by the largest contiguous cluster of protease genes in the human genome, are secreted serine proteases with diverse expression patterns and physiological roles. The aberrant expression of KLK s in various malignancies as well as their involvement in many Cancer-related processes, such as cell growth regulation, angiogenesis, invasion, and metastasis, has prompted scientists to investigate their potential as Cancer Biomarkers. Expression of distinct KLKs is associated with clinicopathological parameters of Cancer patients. Moreover, several KLKs possess signifi cant favorable or unfavorable prognostic value in various malignancies, with prostate-specifi c antigen (PSA) being the most widely used biomarker in clinical practice, today. KLKs are also considered as very promising Biomarkers for Cancer personalized medicine, especially for prediction and monitoring of patients ’ response to chemotherapy, therefore opening up new horizons towards effective patient monitoring post-treatment. This review describes the current status of KLKs as tumor Biomarkers.
Catarina L Silva - One of the best experts on this subject based on the ideXlab platform.
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investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid phase microextraction in combination with gas chromatography mass spectrometry
British Journal of Cancer, 2011Co-Authors: Catarina L Silva, M Passos, Jose S CâmaraAbstract:Investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry
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Investigation of urinary volatile organic metabolites as potential Cancer Biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry
British Journal of Cancer, 2011Co-Authors: Catarina L Silva, M Passos, Jose S CâmaraAbstract:Background: Non-invasive diagnostic strategies aimed at identifying Biomarkers of Cancer are of great interest for early Cancer detection. Urine is potentially a rich source of volatile organic metabolites (VOMs) that can be used as potential Cancer Biomarkers. Our aim was to develop a generally reliable, rapid, sensitive, and robust analytical method for screening large numbers of urine samples, resulting in a broad spectrum of native VOMs, as a tool to evaluate the potential of these metabolites in the early diagnosis of Cancer. Methods: To investigate urinary volatile metabolites as potential Cancer Biomarkers, urine samples from 33 Cancer patients (oncological group: 14 leukaemia, 12 colorectal and 7 lymphoma) and 21 healthy (control group, Cancer-free) individuals were qualitatively and quantitatively analysed. Dynamic solid-phase microextraction in headspace mode (dHS-SPME) using a carboxen-polydimethylsiloxane (CAR/PDMS) sorbent in combination with GC-qMS-based metabolomics was applied to isolate and identify the volatile metabolites. This method provides a potential non-invasive method for early Cancer diagnosis as a first approach. To fulfil this objective, three important dHS-SPME experimental parameters that influence extraction efficiency (fibre coating, extraction time and temperature of sampling) were optimised using a univariate optimisation design. The highest extraction efficiency was obtained when sampling was performed at 50°C for 60 min using samples with high ionic strengths (17% sodium chloride, w v^−1) and under agitation. Results: A total of 82 volatile metabolites belonging to distinct chemical classes were identified in the control and oncological groups. Benzene derivatives, terpenoids and phenols were the most common classes for the oncological group, whereas ketones and sulphur compounds were the main classes that were isolated from the urine headspace of healthy subjects. The results demonstrate that compound concentrations were dramatically different between Cancer patients and healthy volunteers. The positive rates of 16 patients among the 82 identified were found to be statistically different ( P