Acute kidney injury (AKI) is a diverse clinical syndrome and is defined using its unifying features of a sudden loss or substantial reduction in kidney function due to a parenchymal injury caused by circulatory collapse, ischemiareperfusion, systemic inflammatory response syndrome, endogenous or exogenous toxicants or urinary obstructive injury. Over the last decade, the study of biomarkers for acute kidney injury has provided a number of highly promising candidates to aid in the detection, prognostic stratification, and decision-making process for treatment options as well as to provide novel targets for pharmaceutical intervention. This article provides a brief overview over currently available biomarkers for AKI and summarizes recently issued patents in this field. Patents pertaining to diagnosis or detection of AKI as well as patents describing therapeutic strategies based on novel biomarkers of AKI are discussed separately. The article concludes discussing key points and highlighting the limitations of biomarker research and patenting in this field.
Molecularly targeted agents have been successfully introduced into the treatment of patients with cancers. Although, these agents have been shown to improve clinical outcomes for many cancer patients, not all patients benefit from them and a considerable proportion of patients experience severe toxicity that can impair quality of life. To take full advantage of the targeted agents, we need predictive biomarkers of efficacy and toxicity to realize personalized anticancer therapy. However, well-validated biomarkers are currently scarce in targeted therapy, even though the risk of toxicity and high costs cannot be ignored. This article provides a background to biomarkers in molecularly targeted anticancer therapy, and reviews some related patents.
Lung cancer constitutes the leading cause of cancer death worldwide with an overall 5-year survival rate being only 11-14%. As advances in molecular biology reveal the genomic, proteomic and phenotypical heterogeneity of nonsmall- cell lung cancer (NSCLC), it has become evident that treatment strategies should be targeted and tailored to each patient's molecular tumor characteristics. An abundance of prognostic and predictive biomarkers of response to treatment has emerged, with epidermal-growth-factor-receptor tyrosine kinase mutations being the first established predictive biomarker in NSCLC. This review summarizes the relevant patents and most extensively investigated biomarkers in NSCLC over the past ten years and focuses on the recent discovery of several new biomarkers as well as on methodological approaches for the determination of prognosis and prediction of response to specific treatment strategies in NSCLC.
Following the “hierarchy model” of cancer evolution, which describes tumors as assemblies of biologically distinct cells, many researchers have focused on a subpopulation of cancer cells having “stem cell properties” and claimed to be the one that can initiate and maintain tumor growth. Those cells termed “Cancer Stem Cells” (CSCs) or “Cancer Initiating Cells” (CICs) retain the properties of self-renewal, multi-lineage differentiation and tumor initiation in vitro and in vivo and are shown in several cancers to be the cells responsible for long-term maintenance of tumor growth. Additionally, resistance to irradiation and chemotherapy and high frequency of tumor relapse are ascribed to the existence of CSCs within the tumor bulk. Therefore, the idea of selectively targeting CSCs, thus driving to novel approaches in cancer therapeutics, is gaining considerable interest in cancer research field. This review will thereby focus on patents on recent progress in the development of methods for the isolation, purification and preparation of enriched populations of CSCs from tumors. This is based on the expression of biomarkers, such as cell surface antigens, marker genes, miRNAs and transcription factors. In some patent cases, CSCs were detected and isolated based on their different gene expression profiles and signatures. Following CSC biomarker mapping, many inventors proceed to the description of methods using CSCs in assessing the prognosis and treatment of cancer. The granted patents and patent applications reviewed here mainly focus on breast, nervous system and colon cancers.
Human Apurinic/apyrimidinic Endonuclease 1 (APE1) is a key multifunctional protein essential for DNA base excision repair pathway (BER) involved in the repair of DNA base damage caused by alkylating damage and ionising radiation. In preclinical studies, APE1 depletion enhances cytotoxicity of therapeutic agents. Over-expression of APE1 is frequently seen in human tumours and may have prognostic/predictive significance in patients. Preclinical and clinical studies suggest that APE1 is a viable anticancer drug target. In this review, we summarize relevant patents and recent studies that confirm that APE1 is an emerging biomarker, and a promising therapeutic target in cancer.
The integrity of the human genome is threatened by DNA damaging agents, particularly ionizing radiation, which induces potentially lethal double strand breaks. Ionizing radiation is of particular concern given its increasing use in medical diagnostic imaging and given the risk of radiological attack or exposure from nuclear reactor accidents. As biological responses to DNA damage have been elucidated, numerous biomarkers have emerged to potentially serve as biodosimeters of radiation exposure and effects. A brief background on the need for biodosimeters of DNA damage and of the DNA damage response is included. DNA damage biomarkers have many possible applications, including monitoring patients and health care workers exposed in diagnostic imaging, monitoring effectiveness and recovery in patients receiving chemotherapy and/or radiation therapy to inform dosing and scheduling, and establishing individual exposure in populations exposed to a radiological hazard. Recent patents on biomarkers of DNA damage discussed in this review include: antibody based tests of proteins modified in response to DNA damage; RNA and protein marker profiles identified from analysis of genome-wide expression and metabolite screens; and genetic markers of damage sensitivity. Applications, advantages and limitations of each biomarker are discussed.
Acute Kidney Injury (AKI) complicates up to 30% of Intensive Care Unit (ICU) admissions and has been independently associated with increased morbidity and mortality in the critically ill. Current treatment of AKI is frustrated by delay and imprecision in diagnosis when based on traditional biochemical markers of renal function such as serum creatinine. These factors have contributed to the lack of effective interventions to avert or ameliorate AKI. Development of novel urine and blood biomarkers for AKI may allow earlier diagnosis of its occurrence and severity. Clinical application of these biomarkers will meet an unmet need and is likely to greatly influence the management of critically ill patients with, or at risk off AKI in the future. The clinical and commercial importance of this topic is reflected in a large number of recent patent applications in this field. In this review, I discuss evolving technologies for diagnosis of AKI based on a systematic search for recent patent applications or awards regarding biomarkers for diagnosis of acute kidney injury applicable to an intensive care setting.