Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels.

Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC.

Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan.

Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels.

Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.     

Inhibitory effect of Tanshinone IIA on inverted formin-2 protects HaCaT cells against oxidative injury via regulating mitochondrial stress

Context: Epidermal cells play an important role in regulating the regeneration of skin after burns and wounds.

Objective: The aim of our study is to explore the role of Tanshinone IIA (Tan IIA) in the apoptosis of epidermal HaCaT cells induced by H₂O₂, with a focus on mitochondrial homeostasis and inverted formin-2 (INF2).

Materials and methods: Cellular viability was determined using the MTT assay, TUNEL staining, western blot analysis and LDH release assay. Adenovirus-loaded INF2 was transfected into HaCaT cells to overexpress INF2 in the presence of Tan IIA treatment. Mitochondrial function was determined using JC-1 staining, mitochondrial ROS staining, immunofluorescence and western blotting.

Results: Oxidative stress promoted the death of HaCaT cells and this effect could be reversed by Tan IIA. At the molecular levels, Tan IIA treatment sustained mitochondrial energy metabolism, repressed mitochondrial ROS generation, stabilized mitochondrial potential, and blocked the mitochondrial apoptotic pathway. Furthermore, we demonstrated that Tan IIA modulated mitochondrial homeostasis via affecting INF2-related mitochondrial stress. Overexpression of INF2 could abolish the protective effects of Tan IIA on HaCaT cells viability and mitochondrial function. Besides, we also reported that Tan IIA regulated INF2 expression via the ERK pathway; inhibition of this pathway abrogated the beneficial effects of Tan IIA on HaCaT cells survival and mitochondrial homeostasis.

Conclusions: Overall, our results indicated that oxidative stress-mediated HaCaT cells apoptosis could be reversed by Tan IIA treatment via reducing INF2-related mitochondrial stress in a manner dependent on the ERK signaling pathway.     

Circulating microRNAs in human obesity: a systematic review

Context: Differential expression profiles of microRNAs have been reported in human obesity suggesting a miRNAs role in the development of obesity and associated disorders.

Objective: To review circulating microRNAs (c-miRNAs) dysregulated in human obesity and to predict their possible target genes.

Methods: We performed a systematic review on PubMed database (PROSPERO, CRD42017077742) for original works on c-miRNAs and human obesity and recorded c-miRNAs with differential expression profiles. Potential target genes and metabolic pathways for dysregulated miRNAs with at least two independent reports were searched using bioinformatic tools.

Results: Twenty-two c-miRNAs are overexpressed, nine underexpressed and two c-miRNAs dysregulated in both directions in people with obesity compared to lean controls. Bioinformatic analyses suggest these c-miRNAs target on genes associated with fatty acid metabolism and PI3k/Akt pathway.

Conclusion: Literature records 33 c-miRNAs confirmedly dysregulated in human obesity. Their predicted target genes are involved in pathways that could explain the development of obesity and its comorbidities. Further research will clarify the role of these miRNAs on metabolic diseases and their usefulness for the prognosis, prevention and treatment of obesity.     

The pharmacologic characterization of allosteric molecules: Gq protein activation

Context: Drugs such as positive allosteric modulators (PAMs) produce complex behaviors when acting on tissues in different physiological contexts in vivo.

Objective: This study describes the use of functional assays of varying receptor sensitivity to unveil the various behaviors of PAMs and thus quantify allosteric effect through system independent scales.

Materials and methods: Muscarinic receptor activation with acetylcholine (ACh) was used to the demonstrate activity of the PAM agonist 1–(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, Benzyl quinolone carboxylic acid (BQCA) in terms of direct agonism, potentiation of ACh affinity, and ACh efficacy. Concentration–response curves were fit to the functional allosteric model to yield indices of agonism (τ_B), effects on affinity (α cooperativity), and efficacy (β cooperativity).

Results: It is shown that a highly sensitive functional assay revealed the direct efficacy of BQCA as an agonist and relatively insensitive cells (produced by chemical alkylation of muscarinic receptor with phenoxybenzamine) revealed a positive allosteric effect of BQCA on ACh efficacy. A wide range of functional assay sensitivities produced a complex pattern of behavior for BQCA all of which was accurately quantified through the system-independent parameters of the functional allosteric model.

Conclusions: The study of complex allosteric molecules in a range of functional assays of varying sensitivity allows the measurement of the complete array of activities of these molecules on receptors and also better predicts which will be seen with these in vivo where a range of tissue sensitivities is encountered.     

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome.

Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1?C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians.

Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1?C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p?=?0.012 and p?<?0.001, respectively).

Conclusions: Our work showed a significant association between the -1?C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.     

Association between high-sensitivity cardiac troponin T and future cardiovascular incidence in a general Japanese population: results from the Tohoku medical megabank project

Purpose: Elevation of high-sensitivity cardiac troponin T (hs-cTnT) is associated with an increased risk of cardiovascular disease (CVD). This study determined whether hs-cTnT was detectable with N-terminal pro-b-type natriuretic peptide (NT-proBNP) and related to CV risk factors in a general Japanese population.

Materials and methods: The Tohoku Medical Megabank Organization pooled individual participant data for a population-based cohort study in the Iwate prefecture (n?=?30,193, age = 60.2?±?11.5?year).

Results: Hs-cTnT levels were higher in participants with hypertension, diabetes mellitus than in participants without these conditions (all ps < 0.001). Logistic regression analysis demonstrated that NT-proBNP was strongly associated with elevation of hs-cTnT (OR = 3.35, 95% CI = 2.90–3.89, p?<?0.001). The receiver operating characteristic curve analysis showed that hs-cTnT was one of useful biomarker for the differentiation of high risk for CVD (the Suita score ≥ 56) from a general population. Logistic regression analysis demonstrated hs-cTnT levels were related to the CVD high risk group (OR = 2.67, 95% CI = 2.28–3.14, p?<?0.001).

Conclusions: Hs-cTnT levels are associated with elevation of NT-proBNP and high Suita score, which suggests that elevated hs-cTnT is related to subclinical myocardial damage and indicates CV risk.     

Heparanase is a predictive marker for high thrombus burden in patients with ST-segment elevation myocardial infarction

Objective: Heparanase (HPA) is an endo-β-D-glucuronidase capable of degrading heparin sulphate (HS) and heparin side chains. HPA plays a role in tumour growth, angiogenesis, cell invasion and in activation of the coagulation system. We aimed to investigate the relationship between HPA and thrombus burden (TB) in patients with ST-Segment Elevation Myocardial Infarction (STEMI).

Methods: This prospective study enrolled 187 patients with STEMI who were treated with primary percutaneous coronary intervention (pPCI). Blood samples were taken to determine serum HPA levels prior to coronary angiography and heparin administration. Serum HPA analysis was performed with a commercially available Human Elisa kit.

Results: Patients were divided into two groups: high TB (n:58) and low TB (n:129) group. Serum HPA levels were significantly higher in patients with high TB than low TB [250.1 (188.5–338.1) vs. 173.6 (134.3–219.8) pg/mL] (p?<?0.001). Serum HPA levels were higher in patients with no-reflow phenomenon compared with others [(409.3 (375.6–512.5) pg/mL vs. 186.2 (144.2–247.4) pg/mL, p?<?0.001]. In multiple logistic regression analysis HPA was a predictor of high TB.

Conclusion: Elevated HPA level in patients with STEMI is related to high TB. Furthermore, increased HPA level may be associated with thrombotic complications such as no-reflow phenomenon in patients with STEMI.     

CXCR4 as a prognostic biomarker in gastrointestinal cancer: a meta-analysis

Background: CXCR4 is a member of the C-X-C chemokine receptor family, which is associated with multiple types of cancer. Although it has been widely reported, the prognostic value of CXCR4 expression in gastrointestinal (GI) cancer remains controversial.

Methods: A meta-analysis was conducted to investigate the relationship between CXCR4 and prognosis of patients with GI cancer. Subgroup analysis was also performed according to tumour subtypes and heterogeneity test.

Results: A total of 24 studies including 3637 cases suggested that overexpression of CXCR4 is significantly associated with overall survival (OS) for patients with GI cancer (HR = 1.71, 95% CI = 1.45–2.03, p?=?0.000). Subgroup analysis also indicated that high CXCR4 expression in oesophagus, gastric and colorectal cancer all predicted a worse prognosis (HR = 1.52, 95% CI = 1.26–1.84, p?=?0.001 for oesophagus cancer; HR = 1.59, 95% CI = 1.10–2.30, p?=?0.015 for gastric cancer; HR = 2.21, 95% CI = 1.56–3.14, p?=?0.000 for colorectal cancer).

Conclusions: CXCR4 may serve as a prognostic indicator in GI cancer patients.     

Potential use of transrenal DNA for non-invasive monitoring and prognosis of colorectal cancer

Background: Anti-EGFR mAb are recommended treatment for metastatic colorectal cancer (mCRC). Accurate mutation profiling and disease monitoring are challenging. The current study investigates the potential use of transrenal DNA as a biomarker for disease management.

Methods: Agreement between archival tissue specimens and transrenal DNA extracted from 200 post-treated mCRC patients was determined. Total DNA concentrations were measured and mutations within the KRAS and EGFR genes were profiled for each specimen. To ascertain therapy resistance; patients were serially monitored monthly.

Results: Concordance measurement with matched tissues at baseline was remarkably high (92%) for EGFR and KRAS mutations. Sensitivity and specificity were 98.4% and 89.1% respectively. Newly detectable mutations for a subgroup of patients with initial wildtype characteristics were evident after 4?months of anti-EGFR mAb therapy. Survival analysis using adjusted estimates showed that patients detected by transrenal DNA for key mutations or had higher mutant DNA content had poorer outcome.

Conclusion: Transrenal DNA offers new options to follow clinical treatment in mCRC. It demonstrates the ability to capture newly acquired mutations that has strong associative links to therapy resistance. Patients with these mutations fared poorly for survival outcomes and indicated possible prognostic value for transrenal DNA detection.     

Similarities in mRNA expression of peripheral blood drug metabolizing enzymes and cancer marker genes with biopsy samples of head and neck cancer patients

Purpose: To develop peripheral blood mRNA expression profiles of drug metabolizing enzymes (DMEs) as a surrogate to monitor tobacco induced head and neck squamous cell carcinoma (HNSCC), attempts were made to investigate (i) similarities in alterations with the cancer marker genes in biopsy samples and (ii) if alterations similar to that seen in biopsy samples are reflected in peripheral blood.

Methods: Total RNA from eight soft gingival tissues and eight biopsy samples of HNSCC patients and total DNA and RNA from blood of healthy controls (n?=?150) and HNSCC patients (n?=?150) was processed for expression and genotyping studies. Blood from patients receiving chemo-radiotherapy was processed for follow-up study.

Results: qRT-PCR revealed significant increase in mRNA expression of DMEs in biopsy and blood samples of HNSCC patients when compared to controls. Similar alterations were observed in cancer marker genes in these samples. Patients with variant genotypes of DMEs showed greater magnitude of alterations in mRNA expression when compared to wild type controls. Responders of chemo-radiotherapy showed significant decline in induction of mRNA expression of DMEs and cancer marker genes

Conclusions: The data suggest that peripheral blood expression profiles could be used to monitor tobacco-induced HNSCC as well as the treatment response.     

C-Phycocyanin elicited antitumor efficacy via cell-cycle arrest,apoptosis induction,and invasion inhibition in esophageal squamous cell carcinoma

Objectives: Mounting evidence has demonstrated that C-Phycocyanin (C-PC) exhibits marked antitumor activity in a wide type of tumors, such as pancreas cancer, breast carcinoma, lung cancer, and colon cancer. The current study aimed to confirm the antitumor efficacy of C-PC in esophageal squamous cell carcinoma (ESCC).

Methods: The efficacy of C-PC was evaluated against the proliferation of ESCC cell lines EC9706 and EC1 by CCK-8 kit and in a mice model of ESCC EC9706. Cell cycle and apoptosis were investigated by flow cytometry, and cell invasion was determined via transwell chamber. Protein expression was examined by Western blots.

Results: We found that C-PC exhibited anti-proliferation ability in a time-dependent manner and a dose-dependent manner in ESCC EC9706 and EC1 cells. Besides, C-PC markedly arrested cell cycle in the G0/G1 phase, induced cell apoptosis and suppressed cell invasion ability in both EC9706 and EC1 cells (p?<?.01). Notably, C-PC evoked the elevations of Bax, PARP, and cleaved-caspase-3 protein, but reduced cyclin D1, CDK4, Bcl-2, MMP-2, and MMP-9 expression levels. Further investigation from in vivo experiment revealed that C-PC displayed significant antitumor efficacy in the xenografted EC9706 model.

Conclusions: Our data presented herein suggest C-PC exerts antitumor efficacy in ESCC.     

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs.

Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission.

Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p?<?0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity.

Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.     

Tumour expressions of hypoxic markers predict the response to neo-adjuvant chemotherapy in children with inoperable rhabdomyosarcoma

Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS).

Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992–2013).

Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72–125.75; p?=?0.014).

Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.     

Cardiac troponins predict adverse clinical outcomes in stable coronary artery disease: a dose–response meta-analysis of prospective studies

Background: Predictive value of cardiac tropnins (cTns) in stable coronary artery disease (SCAD) has not been fully investigated.

Methods: We performed a meta-analysis to evaluate the dose–response relationship between serum detectable/rising cTns and adverse clinical outcomes, including all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), heart failure (HF) or major adverse cardiovascular events (MACEs) in SCAD.

Results: Sixteen studies involved 34,854 subjects were included. Compared with patients with negative/undetectable cTns, those with rising/detectable cTns were associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the hazard ratio (HR) was 1.83 (95% confidence interval (CI) 1.61–2.08), 2.11 (1.80–2.48), 1.43 (1.26–1.62), 2.36 (1.97–2.83) and 1.99 (1.57–2.53), respectively]. Dose–response analysis have revealed that per 1-SD increment of cTnT was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs [the HR was 1.78 (1.20–2.63), 1.62 (1.41–1.85), 1.26 (1.12–1.42), 1.78 (1.17–2.69) and 1.26 (1.00–1.59), respectively].

Conclusion: Rising/detectable cTns was associated with increased risk of all-cause mortality, CV mortality, MI, HF and MACEs in SCAD in a dose–response manner.     

Global views of proteasome-mediated degradation by mass spectrometry

Introduction: Degradation of proteins by cellular proteasomes is critical for the fidelity of protein homeostasis and proper cell function. Indeed, perturbations in proteasome function, as well as the degradation of specific substrates, are associated with a variety of human diseases. Yet, monitoring and analyzing protein degradation in a high throughput manner in physiology and pathology remains limited.

Areas covered: Here we discuss several of the recently developed mass spectrometry-based methods for studying proteasome-mediated cellular degradation and discuss their advantages and limitations. We highlight Mass Spectrometry Analysis of Proteolytic Peptides (MAPP), a method designed to purify and identify proteasome-cleaved cellular proteins as a novel approach in molecular and clinical profiling of human disease.

Expert opinion: The recent improvement of proteomics technologies now offers an unprecedented ability to study disease in clinical settings. Expanding clinical studies to include the degradation landscape will provide a new resolution to complement the cellular proteome. In turn, this holds promise to provide both new disease targets and novel peptide biomarkers which will further enhance personalized proteomics.     

Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest

Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome.

Methods: Single-center sub-study of 171 patients included in the Target Temperature Management (TTM) Trial randomly assigned to TTM at 33?°C or TTM at 36?°C for 24?h after OHCA. Fragments (tau-A and tau-C) of the neuronal protein tau were measured in serum 24, 48 and 72?h after OHCA. The primary endpoint was neurological outcome.

Results: Median (quartile 1 – quartile 3) tau-A (ng/ml) values were 58 (43–71) versus 51 (43–67), 72 (57–84) versus 71 (59–82) and 76 (61–92) versus 75 (64–89) for good versus unfavourable outcome at 24, 48 and 72?h, respectively (p_group = 0.95). Median tau C (ng/ml) values were 38 (29–50) versus 36 (29–49), 49 (38–58) versus 48 (33–59) and 48 (39–59) versus 48 (36–62) (p_group = 0.95). Tau-A and tau-C did not predict neurological outcome (area under the receiver-operating curve at 48?h; tau-A: 0.51 and tau-C: 0.51).

Conclusions: Serum levels of tau fragments were unable to predict neurological outcome after OHCA.     

Comet assay for assessment of DNA damage in greenhouse workers exposed to pesticides

Purpose: The main goal of the present study was to determine DNA damage in pesticide-exposed greenhouse workers and pesticides non-exposed controls.

Materials and methods: The DNA damage was measured by alkaline comet assay method (pH?>?13) in 41 greenhouse workers and 45 non-exposed individuals as the control. Pesticide exposure was assessed by duration of working in the greenhouse and pesticide application in the greenhouse time. DNA damage was estimated by arbitrary unit and damage frequency.

Results: Arbitrary unit and damage frequency were consistently significantly higher in greenhouse workers than those of the controls (p?=?0.001). In terms of gender in greenhouse, DNA damage of female workers was significantly higher than those in male workers (p?<?0.05). We found significant correlation between DNA damage and working hours spent. Multiple linear regression analysis showed that working hours in the greenhouse as an indication of pesticide exposure were significantly associated with the DNA damage, which can be attributed to the genotoxic potential of the pesticide mixture.

Conclusions: The comet assay is sensitive to detect the damage exposed to chronic effect of pesticides in greenhouse workers. Significant DNA damage was obtained for the exposed group, which was associated with the pesticide exposure.     

Protein interactions study through proximity-labeling

Introduction: The proteome is a dynamic system in which protein-protein interactions play a crucial part in shaping the cell phenotype. However, given the current limitations of available technologies to describe the dynamic nature of these interactions, the identification of protein-protein interactions has long been a major challenge in proteomics. In recent years, the development of BioID and APEX, two proximity-tagging technologies, have opened-up new perspectives and have already started to change our conception of protein-protein interactions, and more generally, of the proteome. With a broad range of application encompassing health, these new technologies are currently setting milestones crucial to understand fine cellular mechanisms.

Area covered: In this article, we describe both the recent and the more conventional available tools to study protein-protein interactions, compare the advantages and the limitations of these techniques, and discuss the recent advancements led by the proximity tagging techniques to refine our conception of the proteome.

Expert opinion: The recent development of proximity labeling techniques emphasizes the growing importance of such technologies to decipher cellular mechanism. Although several challenges still need to be addressed, many fields can benefit from these tools and notably the detection of new therapeutic targets for patient care     

An update on the routine application of MALDI-TOF MS in clinical microbiology

Introduction: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has entered clinical diagnostics and is today a generally accepted and integral part of the workflow for microbial identification. MALDI-TOF MS identification systems received approval from national and international institutions, such as the USA-FDA, and are continuously improved and adopted to other fields like veterinary and industrial microbiology. The question is whether MALDI-TOF MS also has the potential to replace other conventional and molecular techniques operated in routine diagnostic laboratories.

Areas covered: We give an overview of new advancements of mass spectral analysis in the context of microbial diagnostics. In particular, the expansion of databases to increase the range of readily identifiable bacteria and fungi, the refined discrimination of species complexes, subspecies, and types, the testing for antibiotic resistance or susceptibility, progress in sample preparation including automation, and applications of other mass spectrometry techniques are discussed.

Expert opinion: Although many new approaches of MALDI-TOF MS are still in the stage of proof of principle, it is expectable that MALDI-TOF MS will expand its role in the clinical microbiology laboratory of the future. New databases, instruments and analytical software modules will continue to be developed to further improve diagnostic efficacy.     

Proteomics for cancer drug design

Introduction: Signal transduction cascades drive cellular proliferation, apoptosis, immune, and survival pathways. Proteins have emerged as actionable drug targets because they are often dysregulated in cancer, due to underlying genetic mutations, or dysregulated signaling pathways. Cancer drug development relies on proteomic technologies to identify potential biomarkers, mechanisms-of-action, and to identify protein binding hot spots.

Areas covered: Brief summaries of proteomic technologies for drug discovery include mass spectrometry, reverse phase protein arrays, chemoproteomics, and fragment based screening. Protein-protein interface mapping is presented as a promising method for peptide therapeutic development. The topic of biosimilar therapeutics is presented as an opportunity to apply proteomic technologies to this new class of cancer drug.

Expert opinion: Proteomic technologies are indispensable for drug discovery. A suite of technologies including mass spectrometry, reverse phase protein arrays, and protein-protein interaction mapping provide complimentary information for drug development. These assays have matured into well controlled, robust technologies. Recent regulatory approval of biosimilar therapeutics provides another opportunity to decipher the molecular nuances of their unique mechanisms of action. The ability to identify previously hidden protein hot spots is expanding the gamut of potential drug targets. Proteomic profiling permits lead compound evaluation beyond the one drug, one target paradigm.