SETDB1, an H3K9-specific methyltransferase: An attractive epigenetic target to combat cancer.

SET domain bifurcated histone lysine methyltransferase 1 (SETDB1) is an important epigenetic regulator catalyzing histone H3 lysine 9 (H3K9) methylation, specifically di-/tri-methylation. This regulation promotes gene silencing through heterochromatin formation. Aberrant SETDB1 expression, and its oncogenic role is evident in many cancers.

Targeting HIF-2α as therapy for advanced cancers.

Hypoxia-inducible factors (HIF-1α, -2α -3α, and -β) are key factors that control hypoxia-induced carcinogenic pathways. HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer. Oncometabolites, onco-miRNAs, glucose deprivation, pseudohypoxia, cytokine/chemokine secretion, and some unique upstream proteins are involved in the signaling switch from HIF-1α to HIF-2α; thus, understanding this signaling switch is critical for the treatment of advanced cancer.

PLK4: a link between centriole biogenesis and cancer.

Polo like kinase (PLK) is known to play a pivotal role in various cell cycle processes to perpetuate proper division and growth of the cells. Polo like kinase-4 (PLK4) is one such kinase that appears in low abundance and plays a well-characterized role in centriole duplication. PLK4 deregulation (i.

PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis.

Peptidyl arginine deiminase 4 (PAD4) is an enzyme that plays an important role in gene expression, turning out genetic code into functional products in the body. It is involved in a key post translational modification, which involves the conversion of arginine to citrulline. It regulates various processes such as apoptosis, innate immunity and pluripotency, while its dysregulation has a great impact on the genesis of various diseases.

Emerging role of SETDB1 as a therapeutic target.

Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis.

Therapeutical potential of deregulated lysine methyltransferase SMYD3 as a safe target for novel anticancer agents.

SET and MYND domain containing-3 (SMYD3) is a member of the lysine methyltransferase family of proteins, and plays an important role in the methylation of various histone and non-histone targets. Proper functioning of SMYD3 is very important for the target molecules to determine their different roles in chromatin remodeling, signal transduction and cell cycle control. Due to the abnormal expression of SMYD3 in tumors, it is projected as a prognostic marker in various solid cancers.

Focal adhesion kinase inhibitors in the treatment of metastatic cancer: a patent review.

Introduction: Focal adhesion kinase (FAK) plays a prominent role in integrin signaling. FAK activation increases phosphorylation of Tyr397 and other sites of the protein. FAK-dependent activation of signaling pathways implicated in controlling essential cellular functions including growth, proliferation, survival and migration.

Small molecule inhibitors of PIM1 kinase: July 2009 to February 2013 patent update.

Introduction: The proviral insertion in murine (PIM) lymphoma proteins for which three isoforms, PIM1, PIM2 and PIM3 have been identified, belonging to the family of serine/threonine kinases has emerged recently as an important therapeutic target for the development of selective inhibitors as the new drugs for treating hematological malignancies and solid tumors. The small molecules developed by academia and the pharmaceutical industry have steadily increased in the last few years. Several drug discovery groups focus on treating disorders, such as cancer mediated by PIM kinase, have provided preclinical evidence suggesting that PIM inhibitor provides anti-apoptotic activity, inhibit cell survival and cell proliferation.