Current Drug Targets - Volume 15, Issue 1, 2014

Cancer is a consequence of mutations in genes that control cell proliferation, differentiation and cellular homeostasis. These genes are classified into two categories: oncogenes and tumor suppressor genes. Together, overexpression of oncogenes and loss of tumor suppressors are the dominant driving forces for tumorigenesis. Hence, targeting oncogenes and tumor suppressors hold tremendous therapeutic potential f Read More

The breast cancer susceptibility genes BRCA1 and BRCA2 are classic tumor suppressor genes that exhibit an autosomal dominant pattern of inheritance with high penetrance. BRCA carriers inherit one mutant BRCA allele and one wild-type allele; and the wild-type allele is invariably deleted or mutated within the tumor. These genes function as caretakers in the maintenance of genomic stability, in part, by participatin Read More

LKB1 (also known as serine-threonine kinase 11, STK11) is a tumor suppressor, which is mutated or deleted in Peutz-Jeghers syndrome (PJS) and in a variety of cancers. Physiologically, LKB1 possesses multiple cellular functions in the regulation of cell bioenergetics metabolism, cell cycle arrest, embryo development, cell polarity, and apoptosis. New studies demonstrated that LKB1 may also play a role in the maintenance of func Read More

The first DNA mismatch repair gene was identified in Escherichia coli nearly fifty years ago. Since then, five decades of basic biomedical research on this important repair pathway have led to an extensive understanding of its molecular mechanism. The significance of this work was clearly highlighted in the early 1990’s when mutations in the human homologs of the mismatch repair genes were identified as responsible for Read More

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is one of the most frequently disrupted tumor suppressors in cancer. The lipid phosphatase activity of PTEN antagonizes the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to repress tumor cell growth and survival. In the nucleus, PTEN promotes chromosome stability and DNA repair. Consequently, loss of PTEN function increases genomic in Read More

p53 is one of the most important tumor suppressor genes that is frequently mutated in human cancers. Generally, p53 functions as a transcription factor that is stabilized and activated by various genotoxic and cellular stress signals, such as DNA damage, hypoxia, oncogene activation and nutrient deprivation, consequently leading to cell cycle arrest, apoptosis, senescence and metabolic adaptation. p53 not only becomes f Read More

The Adenomatous Polyposis Coli (APC) tumor suppressor is most commonly mutated in colorectal cancers such as familial adenomatous polyposis (FAP); as well as many other epithelial cancers like breast, pancreatic, and lung cancer. APC mutations usually result in a truncated form of the protein lacking the carboxy-terminal region resulting in loss of function. Mutations in APC have been identified in early stages of cancer Read More

Australia is facing a major national medical challenge with the emergence of the Hendra virus (HeV) as a medically and economically important pathogen of humans and animals. Clinical symptoms of human HeV infection can include fever, hypotension, dizziness, encephalitis, respiratory haemorrhage and edema. The window of opportunity for successful patient treatment remains unknown, but is likely to be very narrow. Read More

p53 is one of the main regulators of apoptosis, senescence, cell cycle arrest and DNA repair. The expression, function and stabilization of p53 are governed by a complex network of regulators including p14ARF and MDM2. MDM2 is the main negative regulator of p53 activity and stability. Unlike tumours in adults, which tend to overcome p53 regulation by p53 mutations, the paediatric tumours neuroblastoma and sarcoma frequ Read More

Introduction: Common opioids adverse effects include opioid–induced bowel dysfunction (OIBD), which comprises opioid–induced constipation, dry mouth, nausea, vomiting, gastric stasis, bloating, and abdominal pain. Traditional laxatives which are often prescribed for the prevention and treatment of OIBD possess limited efficacy and display adverse effects. A targeted approach to OIBD management is the use of a combi Read More

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or Read More