The National Cancer Institute's Early Detection Research Network (EDRN) has made significant progress in developing an organized effort for discovering and validating biomarkers, building resources ...to support this effort, demonstrating the capabilities of several genomic and proteomic platforms, identifying candidate biomarkers, and undertaking multicenter validation studies. In its first 10 years, the EDRN went from a groundbreaking concept to an operational success.
The EDRN has established clear milestones for reaching a decision of "go" or "no go" during the biomarker development process. Milestones are established on the basis of statistical criteria, performance characteristics of biomarkers, and anticipated clinical use. More than 300 biomarkers have been stopped from further development. To date, the EDRN has prioritized more than 300 biomarkers and has completed more than 10 validation studies. The US Food and Drug Administration has now cleared 5 biomarkers for various clinical endpoints.
The EDRN today combines numerous collaborative and multidisciplinary investigator-initiated projects with a strong national administrative and data infrastructure. The EDRN has created a rigorous peer-review system that ensures that preliminary data--analytical, clinical, and quantitative--are of excellent quality. The process begins with an internal review with clinical, biostatistical, and analytical expertise. The project then receives external peer review and, finally, National Cancer Institute program staff review, resulting in an exceptionally robust and high-quality validation trial.
Detection of cancer at an early stage when it is still localized improves patient response to medical interventions for most cancer types. The success of screening tools such as cervical cytology to ...reduce mortality has spurred significant interest in new methods for early detection (for example, using non-invasive blood-based or biofluid-based biomarkers). Yet biomarkers shed from early lesions are limited by fundamental biological and mass transport barriers - such as short circulation times and blood dilution - that limit early detection. To address this issue, synthetic biomarkers are being developed. These represent an emerging class of diagnostics that deploy bioengineered sensors inside the body to query early-stage tumours and amplify disease signals to levels that could potentially exceed those of shed biomarkers. These strategies leverage design principles and advances from chemistry, synthetic biology and cell engineering. In this Review, we discuss the rationale for development of biofluid-based synthetic biomarkers. We examine how these strategies harness dysregulated features of tumours to amplify detection signals, use tumour-selective activation to increase specificity and leverage natural processing of bodily fluids (for example, blood, urine and proximal fluids) for easy detection. Finally, we highlight the challenges that exist for preclinical development and clinical translation of synthetic biomarker diagnostics.
For cancer screening to be successful, it should primarily detect cancers with lethal potential or their precursors early, leading to therapy that reduces mortality and morbidity. Screening ...programmes have been successful for colon and cervical cancers, where subsequent surgical removal of precursor lesions has resulted in a reduction in cancer incidence and mortality. However, many types of cancer exhibit a range of heterogeneous behaviours and variable likelihoods of progression and death. Consequently, screening for some cancers may have minimal impact on mortality and may do more harm than good. Since the implementation of screening tests for certain cancers (for example, breast and prostate cancers), a spike in incidence of in situ and early-stage cancers has been observed, but a link to reduction in cancer-specific mortality has not been as clear. It is difficult to determine how many of these mortality reductions are due to screening and how many are due to improved treatments of tumours. In cancers with lower incidence but high mortality (for example, pancreatic cancer), screening has focused on high-risk populations, but challenges similar to those for general population screening remain, particularly with regard to finding lesions with difficult-to-characterize malignant potential (for example, intraductal papillary mucinous neoplasms). More sensitive screening methods are detecting smaller and smaller lesions, but this has not been accompanied by a comparable reduction in the incidence of invasive cancers. In this Opinion article, we focus on the contribution of screening in general and high-risk populations to overdiagnosis, the effects of overdiagnosis on patients and emerging strategies to reduce overdiagnosis of indolent cancers through an understanding of tumour heterogeneity, the biology of how cancers evolve and progress, the molecular and cellular features of early neoplasia and the dynamics of the interactions of early lesions with their surrounding tissue microenvironment.
Summary A vast range of disorders—from indolent to fast-growing lesions—are labelled as cancer. Therefore, we believe that several changes should be made to the approach to cancer screening and care, ...such as use of new terminology for indolent and precancerous disorders. We propose the term indolent lesion of epithelial origin, or IDLE, for those lesions (currently labelled as cancers) and their precursors that are unlikely to cause harm if they are left untreated. Furthermore, precursors of cancer or high-risk disorders should not have the term cancer in them. The rationale for this change in approach is that indolent lesions with low malignant potential are common, and screening brings indolent lesions and their precursors to clinical attention, which leads to overdiagnosis and, if unrecognised, possible overtreatment. To minimise that potential, new strategies should be adopted to better define and manage IDLEs. Screening guidelines should be revised to lower the chance of detection of minimal-risk IDLEs and inconsequential cancers with the same energy traditionally used to increase the sensitivity of screening tests. Changing the terminology for some of the lesions currently referred to as cancer will allow physicians to shift medicolegal notions and perceived risk to reflect the evolving understanding of biology, be more judicious about when a biopsy should be done, and organise studies and registries that offer observation or less invasive approaches for indolent disease. Emphasis on avoidance of harm while assuring benefit will improve screening and treatment of patients and will be equally effective in the prevention of death from cancer.
A comprehensive assessment of ground water resources is carried out in the Ranchi Urban Area to understand the hydrogeochemical processes along with assessment of drinking water quality by means of ...water quality index (WQI). The major chemical composition exhibits that, all major ions are present within the prescribed limits of BIS, 2012. WQI applying quality rating scale to assess the suitability of water for drinking purpose exhibits that 40%, 54.28% and 5.71% of groundwater samples fall within excellent, good and poor water quality, respectively. Elevated concentration of WQI in some locations may be owed to upheaved Sodium, Potassium and Chloride concentrations. In the study area, Ca
2+
-Na
+
-HCO
3
−
, Ca
2+
-Na
+
-Cl
−
and Na
+
-Cl
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were dominant hydrochemical facies. Results of the detailed analysis will contribute in appropriate chemical characterisation and proper management of the vital groundwater resources in the study area.
Prepared by world leaders on this topic, Biomarkers in Cancer Screening and Early Detection offers a comprehensive, state-of-the-art perspective on the various research and clinical aspects of cancer ...biomarkers, from their discovery and development to their validation, clinical utility, and use in developing personalized cancer treatment. * Offers a comprehensive, state-of-the-art perspective on the various research and clinical aspects of cancer biomarkers * Provides immediately actionable information – and hopefully also inspiration – to move discovery and clinical application forward * Offers vital knowledge to help develop personalized cancer treatment for individual patients with specific cancers
Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis ...of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA.
In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20).
For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer.
These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.
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