Recent Patents on Biomarkers - Volume 4, Issue 2, 2014

Nearly hundred years back the first oncovirus Rous Sarcoma Virus (RSV) was isolated. From then onwards, researchers have isolated many viruses associated with human cancer. This review summarizes all the oncoviruses in brief and in detail including Human Papilloma Virus (HPV), Epstein-Barr virus (EBV) and Cytomegalo Virus (CMV). This review also discusses about various past and recent patents published in relation to the above mentioned three oncoviruses. Overall this study focuses on the evolution of oncoviruses.

The oropharyngeal squamous cell carcinomas (OPSCC) are a molecular and clinically heterogeneous group of cancer, not yet fully characterized. The most important risk factors for OPSCC are tobacco and alcohol, however, in the last fifteen years, HPV-positive OPSCC are apparently growing, principally in young male people. It is highly probable that these cases represent a new and particular OPSCC subgroup. A reclassification of OPSCC based in part on the participation of high risk human papillomavirus (HPV) as an etiological factor is likely to be proposed. In addition to the association with HPV, other biomarkers have been added to better understand the OPSCC biological behavior and response to oncologic treatment, including TP53 genotypes or changes in chromosome stability. Of particular interest is the tumor suppressor p16INK4, as its expression levels can function as a surrogate biomarker in the diagnosis of HPV-positive OPSCC. p16INK4 overexpression in combination with the demonstration of HPV active infection, according to most authors may predict a good prognosis, thus p16INK4 has been proposed (and patented) as a therapeutic target in those cancers overexpressing it. This review discusses the recent patents focusing on the p16INK4 diagnostic and prognostic value as well as its possible therapeutic activity.

Head and neck squamous cell carcinomas (HNSCC) are the sixth most common cancers worldwide, accounting for 633000 new cases annually. The etiology of HNSCC is considered to be multifactorial. Smoking and excessive alcohol consumption are well-established risk factors for HNSCCs. Human Papilloma Virus (HPV) particularly subtype 16 has been proposed as a risk factor in Oral squamous cell carcinoma (OSCC) development. Other oncogenic virus species i.e., Epstein Barr Virus and Herpes Simplex Virus Type 1 have also been proposed to be involved in oral carcinogenesis. Recent trends show that there is a decrease in incidence of oropharyngeal squamous cell carcinoma associated with the tobacco use and increase in the HPV associated with OSCC. The identification of HPV in oropharyngeal carcinomas has clinical implications resulting in better prognosis, longer survival and higher rate of response to therapy as compared to HPV negative oral cancer cases. The current paper reviews the different investigative approaches used towards oncoviruses particularly human papilloma virus (subtype-16) using polymerase chain reaction(PCR), in situ hybridization (ISH) technique for HPV DNA, and E6/E7 messenger RNA, with p16 immunohistochemistry (IHC) as a surrogate marker, and also includes the recent patents. An attempt is being made to highlight the advantages and disadvantages of all the diagnostic tests.

Past two decades have seen a tremendous bloom in cancer research, especially considering the biomarkers. Cancer related biomarkers have indeed opened new horizons in the areas of cancer diagnosis, care, therapeutics and prognosis. Oncoviruses and their role in various oral cancers have also been an intensive area of qualitative research. This paper reviews the researches and patents relating to Cytomegalovirus (CMV) as a salivary gland oncovirus. Though the extensive history of its correlation with infectious diseases of salivary glands is well known, its correlation with salivary gland oncogenesis is apparently a new arena of research. This review is an attempt to gather correlations between CMV and salivary gland tumorigenesis. The data were collected using keywords like cytomegalovirus, salivary gland tumors, salivary gland malignancy, patents, biomarkers and oncoviruses through scientific database systems like pubmed, medline, science direct, cochrane library and google scholar. The data published in English language, only for the duration of 1976-2014 were included. The data from other languages and out of the mentioned duration were excluded. Also the search was restricted to patents related to CMV and its association with salivary gland malignancy. Articles related to CMV causing pathologies other than salivary gland pathology were strictly excluded. The authors believe that an inclusive understanding of the biomarkers related to CMV, might help diagnose salivary gland tumors, in addition to opening new vistas of multiple therapeutic alternatives for patient benefit.

A molecular biomarker is an entity whose release, abundance and/or modification state is altered as a result of injury or disease, and can be used to aid diagnosis. The concentrations of injury biomarkers are typically highest within the injured organ, but may be measurable in body fluids. Injuries such as trauma often result in damage to multiple organs, requiring biomarkers that can specifically identify the organs that are injured. Biomarkers such as glial fibrillary acidic protein for brain injury, kidney injury marker-1 for kidney injury, cardiac troponin for heart damage, intestinal-type fatty acid binding protein for gut injury, and d-dimer for coagulopathy have been shown to have clinical diagnostic utility to detect injury to individual organs. The long-term objective of injury-associated biomarker research is to identify and validate a panel of biomarkers to diagnose (or exclude) injury to various organs and/or predict ensuing symptoms/outcome. Unfortunately, such a panel is not currently available. This review will critically assess the current status and related patents of individual biomarkers being investigated for the diagnosis of injury to specific organs, and discuss the feasibility of generating a panel of biomarkers that can be used to diagnose injury to multiple organs.

Helicobacter pylori are the main cause of gastritis, peptic ulceration and distal gastric adenocarcinoma. Bacterial virulence factors actively contribute in the clinical outcome and progression of Helicobacter pylori infection. The wide range of digestive disease attributed with Helicobacter pylori infection has led scientists to a huge interest in biomarkers. Thus, determination of a biomarker as practical patent for each infectious disease needs a logical clinical set up. Identification of a validated biomarker for Helicobacter pylori calls further investigations including in vitro and in vivo experiments. Undoubtedly, determination of best available biomarker such as dupA can help physicians to go one step further to manage persistent colonizsation of Helicobacter pylori.

Preeclampsia is an important cause of morbidity and mortality of mother and fetus. Preeclampsia is characterized by hypertension and proteinuria occurring during the last trimester of pregnancy. In this review, an attempt is be done to discuss mechanisms of preeclampsia with an emphasis on diagnostic markers of preeclampsia and its complications along with patents available in this aspect.

Background: Metastatic Renal Cell Carcinoma (mRCC) is a malignancy with a poor prognosis due to inefficacy of chemotherapy and to the efficacy of immunotherapy only in few patients. The availability of agents directly targeting tumorigenic and angiogenic pathways, as Vascular Endothelial Growth Factors (VEGF) inhibitors, has significantly improved the outcome of these patients. Aim of this work is to evaluate the possible prognostic and predictive role of patent biomarkers on mRCC. Methods: We have done a critical review based on Level of Evidence (LOE) analysis of recent publications indexed on PubMed from January 2011 up to August 2014. These studies have evaluated whether biomarkers can have a correlation with clinical outcomes in metastatic RCC patients treated with VEGF-targeted therapy. Results: We identified a total of 25 articles. On the basis of results of randomized controlled trials and prospective and retrospective observational studies, we tried to assess the predictive role of biomarkers. Six of these biomarkers (VEGF, interleukin (IL)-6, hepatocyte growth factor (HGF), osteopontin, IL-8 and sVEGFR-3) showed a potential predictive role. Moreover, VEGF-A, IL-6 and IL-8 seem to have prognostic value. Conclusion: Despite intensive efforts, there are no validated predictive or prognostic biomarkers currently in use in patients with mRCC. This literature up date is trying to highlight the biomarkers potentially useful to predict response to VEGF-targeted therapy and those with a prognostic value.