Current Drug Targets - Volume 12, Issue 14, 2011

Welcome to this special issue of Current Drug Targets in which we review some of the very promising new targets and therapeutic approaches which epitomize the drive towards personalized, molecular-based anti-cancer care. The spectrum of targets we discuss include kinases, chaperone proteins, receptors and enzymes. The aurora family of serine/threonine kinases, essential for chromosome alignment, segregation and Read More

Heat shock proteins (Hsp) are highly conserved proteins and their expression is dependent on the level of various cellular stresses. Hsp work as a molecular chaperon for several cellular proteins and have cytoprotective roles. Their function is essential for normal cell viability and growth. Hsp90 interacts with proteins mediating cell signaling involved in essential processes such as proliferation, cell cycle control, angiogenesis and Read More

Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic paradigms based on similarities, differences and interactions with current standard of care agents. In par Read More

Insulin-like growth factor type-1 receptor (IGF-1R) plays a central role in cell proliferation and survival and is overexpressed in many tumor types. Notably, IGF-1R-mediated signaling confers resistance to diverse cytotoxic, hormonal, and biologic agents, suggesting that therapies targeting IGF-1R may be effective against a broad range of human malignancies. Cixutumumab (IMC-A12; ImClone Systems) is a fully human immuno Read More

Poly(ADP-ribose) polymerase (PARP) is a critical DNA repair enzyme involved in DNA single-strand break repair via the base excision repair pathway. PARP inhibitors have been shown to sensitize tumors to DNA-damaging agents and to also selectively kill homologous recombination repair-defective cancers, such as those arising in BRCA1 and BRCA2 mutation carriers. Recent proof-of-concept clinical studies have demonstra Read More

The hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-MET) receptor tyrosine kinase (RTK) pathway plays a pleotropic role in cell proliferation, migration, invasion, angiogenesis and survival. Although it has critical physiological functions in embryonic development and tissue repair, this signaling cascade is frequently deregulated in a wide range of tumors. Aberrant HGF/c-MET signaling, driven by variou Read More

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins a Read More

The Aurora family of serine/threonine kinases is essential for chromosome alignment, segregation, centrosomal maturation, mitotic spindle formation, and cytokinesis during mitosis. Their fundamental role in cell cycle regulation and aberrant expression in a broad range of malignancies prompted the development of small molecules that selectively inhibit their activity. Recent studies have revealed new insights into the ce Read More

Tumor necrosis factor-related apoptosis-inducing ligand or Apo2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis upon binding to its death domain-containing transmembrane receptors. The preferential toxicity of TRAIL to cancer cells and the sparing of normal cells make it an ideal cancer therapeutic agent. TRAIL induces apoptosis via the extrinsic death receptor apoptotic Read More

Contrary to the Classical Greek poet Archilochus' phrase “The fox knows many things but the hedgehog knows one big thing”, the Hedgehog (HH) signaling pathway knows at least 3 ways to promote or support carcinogenesis. In this review, we provide a summary of the HH signaling pathway, and detail the clinical relevance and treatment of patients. Finally, future directions in exploiting this promising pathway will be addressed.

Recent meta-analyses have revealed that the risk of bone fracture is increased in both type 1 and type 2 diabetic patients. Low bone mineral density (BMD) can not necessarily explain the link, because BMD is increased rather than decreased in type 2 diabetes, while it is consistently low in type 1 diabetes subjects. Although multiple factors could influence the quality of bone and increase the bone fragility in diabetes, there i Read More

Obesity and degenerative joint disease (osteoarthritis, OA) are two multifactorial pathologies that are becoming major medical issues with the aging of the world population. The relationship of OA with obesity is complex, involving both biomechanical and metabolic links. Dysregulated production of adipose tissue-derived inflammatory mediators, hyperlipidemia, and increased systemic oxidative stress are conditions fre Read More

Malaria has emerged as one of the most debilitating parasitic infection with about 500 million cases reported annually and one million deaths worldwide. Currently, Plasmodium falciparum has developed resistance to almost all classes of antimalarials, thus precluding the use of those agents which once formed the cornerstone of malaria therapy. In lieu of this phenomenon, and taking into consideration the absence of Read More