In recent years, spectacular advances in understanding of molecular mechanism of cancer progression have revolutionized the way we see the process of malignant transformation and we are waiting for this knowledge to be translate in better treatments for cancer patients. This progress has attracted the interest towards the development of targeted therapies for cancer and creates the basis for the so called “personalized medicine”. However, this advancement has not been paralleled by discoveries in the field of biological indicators, or molecular biomarkers, able to implement the targeted therapies.

Biomarkers that indicate biological activity and/or efficacy are a potentially useful tool in the development of molecularly targeted therapeutics. Most pharmacodynamic assays measure the response to drugs in tissues, a procedure requiring tissue biopsies, which is often not available. In this study, we identify GDF15 as a potential plasma biomarker for Danusertib (formerly PHA-739358), an Aurora kinase inhibitor, currently in phase I/II clinical studies. Cell lysates and cell-free culture supernatants from human tumor isogenic cell lines were assessed for GDF15 levels following treatment with Danusertib, by using Western Blotting and Elisa. GDF15 levels were also measured in plasma from xenografted mice as well as in plasma from patients before and after Danusertib treatment. At the protein level an increased level of GDF15 was found in tissue culture cells after Danusertib treatment and GDF15 expression was also detected in plasma of xenografted mice treated with the compound. Hence, both cellular and xenograft models of human cancer showed a clear correlation with p53 pathway activation. Danusertib treatment also resulted in a significantly increased expression of GDF15 protein levels in the plasma of examined patients, underlining technical feasibility of translating this putative biomarker to clinical studies. Determination of GDF15 levels in plasma is feasible and enabled us to follow the kinetic of Danusertib activity in plasma from cancer xenografted mice and from patients. These findings should allow us to evaluate systematically the kinetics of p53 activation by Danusertib in future clinical studies.

Oxidatively induced DNA damage is caused by endogenous and exogenous sources in living organisms. Many resulting DNA lesions are mutagenic and lead to mutations commonly found in cancer. Repairs mechanisms exist to repair this type of DNA damage. Unrepaired and accumulated DNA lesions may lead to carcinogenesis and other disease processes. Defects in DNA repair are associated with cancer. Oxidatively induced DNA lesions accumulate in cancerous tissues, possibly contributing to genomic instability and metastatic potential. Recent evidence suggests that some tumors may even possess increased DNA repair capacity, leading to therapy resistance. DNA repair inhibitors are being developed to target the repair pathways and increase the efficacy of cancer therapy. Oxidatively induced DNA lesions and DNA repair proteins are potential biomarkers for early detection, cancer risk assessment, prognosis and monitoring the therapy. Overall, accumulated evidence suggests that oxidatively induced DNA damage and its repair are important factors in carcinogenesis, and deserve more research to understand and fight cancer.

Gastric cancer is the second cause of cancer deaths in China. To identify potential markers for screening or diagnosis of gastric cancer, we coupled xenotransplantation mouse models with a urine metabolomic approach. SGC-7901 gastric cancer cells were subcutaneously or orthotopically implanted into nude mice to establish metastasis and non-metastasis mouse models. Urine samples from mice bearing tumors or gastric cancer patients and their healthy controls were collected and subjected to gas chromatography and mass spectrometry (GC/MS) analysis. Metabolic data were analyzed using Mann-Whitney test to find urinary biomarkers for gastric cancer. Diagnostic models for gastric cancer mice and patients were constructed using principal components analysis (PCA) and validated with the area under the curve (AUC) of receiver operating characteristic (ROC) curves. The results indicated these metabolites mainly include lactic acid, serine, proline, malic acid, and fatty acids. The PCA models discriminated all gastric cancer mice or most gastric cancer patients including six of seven early stage patients, from their healthy controls with AUC value of 1.0 or 0.996, respectively. In addition, they were able to differentiate between metastatic and non-metastatic mice with AUC value of 1.0, as well as between invasive/metastatic and non-invasive cancers with AUC value of 0.982. Our data suggest that there are significant metabolic alterations during progression of gastric cancer and the potential metabolic biomarkers could be useful for screening and early diagnosis of gastric cancer progression.

Ovarian cancer is a very aggressive disease that is mostly asymptomatic at early onset. Approximately 85% of patients are diagnosed at late-stage disease, which greatly compromises full recovery. Standard detection methods include measurement of the ovarian cancer biomarker CA-125. However, CA-125 is associated with false positive diagnosis and is largely limited to late-stage disease. As a result, there is a great need to discover new biomarkers and develop novel detection and imaging methods for ovarian cancer. Patients with ovarian cancer often respond to initial chemotherapy but most will succumb to recurrent disease. Such poor prognosis is associated with a drug resistant subpopulation of cancer cells with stem-like properties known as cancer stem cells (CSC). Traditional chemotherapy fails to target CSC, and it is widely accepted that this process leads to the recurrence of more aggressive tumors. Therefore, it is essential to discover new ovarian CSC biomarkers and develop therapies that specifically target this subpopulation. Bacteriophage (phage) display technology allows identification of high affinity peptides by screening of peptide libraries against cellular targets. The large amount of unique peptides in a library facilitates high throughput selections both in vivo and in vitro. Here we discuss how phage display can be utilized to discover novel peptides with high binding affinity for normal ovarian cancer cells and ovarian CSC. Such peptides may be radiolabeled and employed in SPECT and PET imaging as well as in therapeutic settings. Further, both phage and phage display derived peptides can be employed in identification of targeted antigens and novel ovarian cancer biomarkers using mass spectrometry analysis. Such biomarkers may be utilized in diagnosis and in identification and selection of ovarian cancer subpopulations.

The incidence of clear cell renal cell carcinoma (ccRCC) continues to increase while very few treatment options are available for therapy. Development of metastatic disease dramatically decreases patient survival; therefore detection at an early stage while still localized to the renal capsule is imperative for a favorable prognosis. With recent advances in molecular technologies and subsequent understanding of the underlying pathology of disease, molecular markers have been defined that are predicative of tumor stage, metastatic potential and patient prognosis. Analysis of these biomarkers along with current staging techniques already used in the clinic may allow for implementation of personalized post-surgical treatment plans as well provide further molecular pathways for targeted therapeutic interventions. In this review we will highlight the potential ccRCC biomarkers that have been identified through a variety of molecular techniques to date, and provide insight into research models for biomarker discovery.

The discovery and characterization of genes and molecules involved in oral carcinogenesis have contributed to the diagnosis, assessment of prognosis and survival of patients with oral cancer. The knowledge of etiological and biological mechanisms involved in cancer allows important advances in diagnosis and therapeutics. Numerous parameters are used to measure the aggressiveness of a tumor, among which cell proliferation stands out, an important phenomenon related to the behavior of lesion and that is linked to dysregulation of the cell cycle machinery in various cancers. Scientific researches have been conducted to investigate these events. This review discusses the use of cell proliferation markers in oral cancer, particularly oral squamous cell carcinoma, emphasizing those related to cell proliferation rate, such as PCNA, Ki-67, AgNORs, cyclins, MCM and geminin. Criteria used for diagnostic and prognostic such as clinical stage, size and location of lesions, margin of lesions, associated with the use of these biomarkers offer valuable opportunities to evaluate the behavior of the disease and, moreover, are of great prognostic value.

Background: The level of β2-M has become one of the most important prognostic factors and predictors of survival in patients with certain caner. The aim of this study was to investigate the serum levels of β2-M in patients with various solid cancers, to find the prognostic and predictive value of serum β2-M level elevating in patients with solid cancer. Methods: A total of 1158 serum from 774 patients with various solid cancer and 384 patients with various solid benign tumor patients were analyzed by β2-microglobulin ELISA kit, the data were analyzed by using statistical 36 packages for sciences (spss11.0) software. Results: In patients with thyroid cancer, patients with breast cancer and that with liver cancer the mean β2-microglobulin levels and positive rate were significantly higher than that in controls (p<0.05, p<0.01). In patients with other solid cancer including gastric, esophagus, intestinal and lung cancer the mean β2-microglobulin levels have no significant difference compared with that in controls (p>0.05), and the positive rats were not significantly different compared with that in controls (p>0.05) except the patients with esophagus cancer in which the positive rate was significantly different compared with that in controls (p < 0.01). In female breast cancer patients the mean β2- microglobulin levels and the positive rate were significantly higher than that in breast benign tumor patients (p<0.05: p<0.05), no significant difference stages and clinical stages. In thyroid cancer patients the mean β2-microglobulin levels and the positive rate were significantly higher than that in thyroid benign tumor patients (p< 0.05, p< 0.01), no significant difference in sex, ages, clinical stages, but the mean β2-microglobulin levels and the positive rate were significantly higher in patients with follicular thyroid cancer than that in patients with mamillary thyroid 54 cancer patients. Conclusion: β2-M is an important tumor marker in breast, thyroid and liver cancer that would be one of assistantly diagnostic factors in patients with these cancers.

In neuroblastoma (NB), age at diagnosis is a strong prognostic factor. Hereby, we evaluated whether patients with metastatic NB below 1 year of age (infants) expressed lower levels of NB-specific molecular markers compared to patients over 1 year (children). Bone marrow (BM) and peripheral blood (PB) samples collected at diagnosis from 54 Italian patients with metastatic NB were analysed by RT-qPCR for TH, PHOX2B and DCX mRNA expression. Statistical analyses were then performed to evaluate the diagnostic performance and the association with other known prognostic factors. In spite of similar levels of morphological BM infiltration, TH, PHOX2B and DCX �?¯ï¿½?�?��? expression levels in BM and PB samples were significantly lower in stage 4 infants than in children. Between infants with stage 4 and 4S, the former expressed significantly higher levels in BM samples but similar levels in PB samples. In children with stage 4 NB, TH expression levels significantly associated with the presence of BM and skeletal metastasis. Thus, RT-qPCR analysis of BM and PB samples showed potential clinical significance that should be evaluated in future multicentre prospective studies for infants with metastatic NB in comparison with conventional morphological evaluation and other prognostic factors evaluable in the primary tumors.

Circulating extracellular nucleic acids, especially DNA, was discovered more than sixty years ago, but it is becoming hot just in the last two decades because it is now widely recognized as a very promising biomarker for the early diagnosis, monitoring, and evaluation of prognosis of cancer. In addition, compared with traditional surgical approaches and other biochemical tests, circulating DNA as a biomarker, owns many obvious advantages. It is easily accessible, reliable, reproducible and early detectable in cancer. It is also very sensitive and specific if cancer specific DNA alterations are tested instead of elevation of circulating DNA concentration. But the clinical application of this biomarker is still just limited to obstetrics and prenatal diagnosis. This review throws light on its history, current research update and potential clinical application in cancer diagnosis and management. In addition, major detection technologies of circulating DNA are summarized concisely and comprehensively.