Current Drug Targets - Volume 11, Issue 1, 2010

Despite significant advances in the treatment of non-small cell lung cancer (NSCLC) over the past several years, the prognosis for patients with advanced disease is still very poor. NSCLC patients treated with standard regimens containing cisplatin or carboplatin have a median survival of 8-11 months for patients with Stage IV disease and 5-7 months for patients with relapsed disease. Evaluation of new treatment strategies i Read More

Pemetrexed is a novel third-generation multitargeted antifolate agent used in the first- and second-line treatment of unresectable pleural mesothelioma and advanced non-small cell lung cancer (NSCLC). Owing to its mild toxicity, this compound is a preferred partner in the multidrug regimens. In the last few decades, better understanding of molecular oncology and genetics has allowed for the development of an arra Read More

Conventional regimens have limited impact against NSCLC. Current research is focusing on multiple pathways as potential targets, and this review describes pharmacological aspects underlying the combination of the PKCβ-inhibitor enzastaurin with the multitargeted antifolate pemetrexed. Pemetrexed is commonly used, alone or combined with platinum compounds, in NSCLC treatment, and ongoing studies are evaluating it Read More

The incidence of lung cancer in 2007 is estimated to be 213,380 with 160,390 deaths in the United States. It contributed to 31% of male and 26% of female cancer-related deaths and is the largest cause of cancer-related mortality in both men and women. Despite some advances in the treatment of advanced non-small cell lung cancer (NSCLC), the introduction of third-generation cytotoxic agents (vinorelbine, gemcitabi Read More

Pemetrexed is a newer antifolate drug that has been approved as first-line treatment for patients with advanced non-squamous, non-small cell lung cancer (NSCLC) in combination with cisplatin, and as single agent for relapsed or chemotherapy refractory NSCLC after platinum-containing chemotherapy, at a dose of 500 mg/m2. Pemetrexed undergoes intracellular activation by poly-γ-glutamylation, that is essential for its a Read More

Pemetrexed is a multi-targeted anti metabolite that inhibits several key folate-dependent enzymes in the thymidine and purine biosynthetic pathways, including thymidylate synthase. It is currently approved for use in patients with non-small cell lung cancer and malignant mesothelioma. The sporadic and unpredictable occurrence of haematological toxicities of pemetrexed leading to potentially life threatening complicatio Read More

Despite improvements in first-line therapy for advanced NSCLC all patients with metastatic disease will progress at some point. Patients with favorable prognostic factors such as good performance status, non-squamous histology, stable weight, and perhaps female gender are more likely to receive second-line chemotherapy. Currently the United States FDA recognizes three single agents (docetaxel, erlotinib, and pemetre Read More

Pemetrexed is a multitargeted antifolate that inhibits at least three folate dependent enzymes involved in DNA synthesis. Gemcitabine is a broadly active pyrimidine nucleoside antimetabolite that is incorporated into DNA and causes chain termination. Both pemetrexed and gemcitabine, as single agents, have shown antitumor activity in a wide range of solid tumors, including non-small-cell lung cancer (NSCLC). Based on pre Read More

Approximately one out of every three patients with non-small cell lung cancer (NSCLC) has locally advanced disease that is surgically unresectable. If their performance status allow, it is current practice to treat these patients with a combination of chemotherapy and external beam irradiation. There have been several studies supporting the addition of chemotherapy to radiation, particularly when delivered concurrently. There i Read More

Bronchioloalveolar carcinoma (BAC) and adenocarcinoma with bronchioloalveolar features (ADC-WBF) belong to the same anatomo-clinical entity and show very similar epidemiologic, clinical and biological characteristics. However there is a lack of consensus for the treatment of unresectable forms. Although epidermal growth factor receptor tyrosine kinase inhibitors and paclitaxel do have some efficacy, the aim of this review Read More

Platinum-based doublet chemotherapy is now established as a standard of care in the adjuvant treatment of resected stage II and stage IIIA nonsmall cell lung cancer, and seems reasonable also in resected stage IB when the primary tumor measures ≥4 cm. Several issues remain unresolved, however, including individualized selection of both the optimal platinum (cisplatin vs carboplatin), and the optimal nonplatinu Read More

Both the multi-targeted antifolate pemetrexed and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib have established roles in the treatment of advanced non-small cell lung cancer (NSCLC). Given different mechanisms of action and minimal overlapping toxicities, combinations of these agents have been considered. However, four previous phase III trials investigating concurrent chemoth Read More

Despite recent advances, treatment of leukemia is often not curative. New insights indicate that this may be attributable to a small population of therapy-resistant malignant cells with self-renewal capacity and the ability to generate large numbers of more differentiated leukemia cells. These leukemia-initiating cells are commonly referred to as Leukemia Stem Cells (LSCs). LSCs are regarded as the root of leukemia origin and l Read More

Coenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of CoQ10 in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit Read More

White adipose tissue (WAT) is an important endocrine organ that secretes approximately 30 biologically active peptides and proteins, collectively termed “adipokines”. These are either produced exclusively by WAT (mainly adiponectin, leptin and resistin) or also by other tissues [e.g. tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, plasminogen activator inhibitor (PAI)-1, angiotensinogen]. Adipokines play a central role in Read More