Current Protein and Peptide Science - Volume 22, Issue 7, 2021

Epithelial ovarian cancer (EOC) is a chronic and degenerative disease propelled by a mutation in BRCA1/2 genes, familial history, smoking and polycystic ovary syndrome. Although the lifetime risk of ovarian cancer is low, yet it is the fifth leading cause of cancer-related deaths. Surprisingly, EOC represents 90% of all ovarian cancers, out of which 70% of women are diagnosed with the malignancy at its advanced III-IV stages. Early detection may increase the life expectancy up to 5 years. Thus, it has become the need of the hour to attain improvement of clinical outcomes of EOC and improve the life expectancy of patients. A plethora of proteins in different biological fluids may serve as prospective identifiers for the disease. Over the years, accurate identification of proteins secreted by EOC cells has been perfected by in vitro and in silico state-of-theart technologies. Multivariate test, consisting of histo-pathological data in combination with protein biomarker panel has paved way for enhanced and accurate assessment of EOC; still, there is a chance of further improvement. This review encompasses the advances made in ovarian cancer biomarker discovery and demonstrates their potential usefulness for the design of early diagnostics of EOC.

Enzyme prodrug therapy has gained momentum in recent years due to its ability to improve therapeutic index (benefits versus toxic side-effects) and efficacy of chemotherapy in cancer treatment. Inactive prodrugs used in this system are converted into active anti-cancerous drugs by enzymes, specifically within the tumor cells. This therapy involves three components namely prodrug, enzyme and gene delivery vector. Past reports have clearly indicated that the choice of enzyme used is the major determinant for the success of this therapy. Generally, enzymes from nonhuman sources are employed to avoid off-target toxicity. Exogenous enzymes also give better control to the clinician regarding the calibration of treatment by site-specific initiation. Amongst these exo-enzymes, microbial enzymes are preferred due to their high productivity, stability and ease of manipulation. The present review focuses on the commonly used microbial enzymes, particularly cytosine deaminase, nitroreductase, carboxypeptidase, purine nucleoside phosphorylase in prodrug activation therapy. Various aspects viz. source of the enzymes, types of cancer targeted, mode of action and efficacy of the enzyme/prodrug system, efficient vectors used and recent research developments of each of these enzymes are comprehensively elaborated. Further, the results of the clinical trials and various strategies to improve their clinical applicability are also discussed.

Neurodegenerative diseases have emerged as one of the major age-associated diseases in recent years. Hence, the urge to understand the mechanism and to find targeted therapeutics becomes inevitable. Peptide-based compounds have emerged as one of the important tools for their therapy. However, due to a lack of tolerability, specificity, and proteolytic degradation, they have lost their applicability in the broader sense. Thus, the search for suitable alternatives or peptidomimetics becomes an important criterion for neurotherapeutics. One of the versatile peptidomimetics is N-substituted glycines or peptoids, which retain many properties of peptides but successfully evade the drawbacks of peptides. Peptoids are manifested with greater cellular permeability, less immunogenicity, and their ability to be administered intra-nasally. These properties enhance their potential as neurotherapeutics with respect to their peptide counterparts. Recently, peptoids have been explored for neurotherapeutic applications as aggregation inhibitors, cell signaling pathways modulators, and agents for inhibiting inflammation via multiple mechanisms. Peptoids, due to their versatility and low production cost, are becoming popular among peptidomimetics as potential neurotherapeutic agents. In this review, the diverse applications of peptoids with respect to neurodegenerative disease have been explored.

As a major threat among women globally, breast cancer (BC) emerges as a primary research focus for several researchers. Although various therapeutic regimens are available, there is an increased chance of metastasis of BC cells, which raises the severity of this malignancy. Of multiple preferred secondary targets, metastasis to bone is extensively studied. Besides deemed as a bone transcription factor, Runx2 also acts as a metastatic factor that promotes growth and metastasis of BC cells. Studies have reported the significant role of microRNAs (miRNAs) in BC pathogenesis and metastasis by governing Runx2 expression. Additionally, dysregulation of the signaling pathways, including Wnt/β-catenin, TGF-β, Notch, and PI3K/AKT, has been observed to influence the expression of Runx2 in BC cells. In this review, we have aimed to highlight the regulatory role of miRNAs in targeting Runx2 both directly and indirectly by governing respective signaling pathways during bone metastasis of BC.

Post Translational Modification (PTM) is a process in which covalent addition of functional groups on protein occurs to maintain their structure, function and stability. Every PTM process in our living system occurs to enhance the functional diversity of a protein. But sometimes, it occurs without any regulation and that might lead to autoimmunity. Rheumatoid arthritis (RA) is one such chronic, inflammatory, autoimmune disease that affects the joints. Proper treatment can make the symptoms manageable for RA, but it is not curable. Delayed diagnosis of RA can cause severe bone pain, stiffness, inflammation, redness in joints and affect other parts of the body such as the liver, kidney, etc. Early diagnosis of RA is necessary to manage the aggressive symptoms. Currently, Rheumatoid factor (RF) and anti-citrullinated cyclic peptide (Anti-CCP) are considered as biomarkers to diagnose RA. Besides citrullination, several other PTMs are also involved in the generation of autoantibodies, such as carbamylation, glycosylation, glycation, acetylation, ubiquitination, proteolysis, phosphorylation, and lipidation. The aim of this review is to elucidate several changes in the form, nature, and function of PTMs in RA. This review will give a recent overview on the role of PTMs in the pathogenesis of RA with a focus on the post-translational modifications.

Eukaryotic translation initiation factor 4A (eIF4A) is a highly conserved DEAD-box RNA helicase in eukaryotes with ATPase and RNA helicase activities. eIF4A plays an important role in capdependent translation at the initiation of mRNA translation, and carcinoma signal transduction pathways are focused on cap-dependent translation. eIF4A is highly expressed in a variety of cancers, and its high expression is associated with the degree of leukemia progression. Therefore, eIF4A, as a target for tumor therapy, has become a hot research topic. Many small-molecule inhibitors targeting eIF4A have been demonstrated in preclinical cancer model trials. The purpose of this review is to describe the function of eIF4A and the development of eIF4A targeting inhibitors.