Cancer patients spontaneously generate autoantibodies (AAb) to tumor-derived proteins.. To detect AAb, we have probed novel high-density custom protein microarrays (NAPPA) expressing 4,988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and bound IgG was measured. We used a three-phase serial screening approach. First, a pre-screen was performed to eliminate uninformative antigens. Sera from stage I–III IBC (n=53) and healthy women (n=53) were screened for AAb to all 4,988 protein antigens. Antigens were selected if the 95th percentile of signal of cases and controls were significantly different (p<0.05) and if the number of cases with signals above the 95th percentile of controls was significant (p<0.05). These 761 antigens were screened using an independent set of IBC sera (n=51) and sera from women with benign breast disease (BBD) (n=39). From these, 119 antigens had a partial area under the ROC curve (p<0.05), with sensitivities ranging from 9–40% at >91% specificity. 28 of these antigens were confirmed using an independent serum cohort (n=51 cases/38 controls, p<0.05). Using all 28 AAb, a classifier was identified with a sensitivity of 80.8% and a specificity of 61.6% (AUC=0.756). These are potential biomarkers for the early detection of breast cancer.

Pseudomonas aeruginosa is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis. P. aeruginosa infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported P. aeruginosa PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant (P < 0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.

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Searching for targets that allow pharmacological inhibition of cell proliferation in over-proliferative states, such as cancer, leads us to finely understand the complex mechanisms orchestrating the perfect control of mitosis number, frequency and pace as well as the molecular arrangements that induce cells to enter functional quiescence and brings them back to cycling in specific conditions. Although the mechanisms regulating cell proliferation have been described several years ago, never before has so much light been shed over this machinery as during the last decade when therapy targets have been explored and molecules, either synthetic or in the form of antibodies with the potential of becoming cancer drugs were produced and adjusted for specific binding and function. Proteins containing tyrosine kinase domains, either membrane receptors or cytoplasmic molecules, plus the ones activated by those in downstream pathways, having tyrosine kinase domains or not, such as RAS which is a GTPase and serine/threonine kinases such as RAF, play crucial role in conducting proliferation information from cell surroundings to the nucleus where gene expression takes place. Tyrosine kinases phosphorylate tyrosine residues in an activating mode and are found in important growth factor receptors, such as for ligands from families collectively known as VEGF, PDGF and EGF, to name a few and in intracellular downstream molecules. They all play important roles in normal physiology and are commonly found mutated or overexpressed in neoplastic states. Our objective here is to present such kinases as druggable targets for cancer therapy, highlighting the ones for which the pharmacological arsenal is available, discussing specificity, resistance mechanisms and treatment alternatives in cases of resistance, plus listing potential targets that have not been successfully worked yet.