Current Clinical Pharmacology - Volume 5, Issue 3, 2010

In several Western countries cancer has passed cardiovascular diseases of the top-3 causes of death and now heads the charts. Better treatment options and preventive measures in cardiovascular medicine have resulted in its sharp decrease of death rate. Part of the explanation, however, is that cancer incidence is still rising every year. This is primarily due to the proportional increase of the ageing population, with cancer bei Read More

Personalized treatments with molecularly targeted agents are considered new and heading towards a bright future in medical oncology. The development of imatinib was a landmark and its clinical and commercial success revolutionized many new developments in this area. Molecular targeted therapies require strict patient selection to identify those who may benefit. Novel targeted (personalized) therapies with antibo Read More

This review focuses on the development of monoclonal antibodies that have been or are being introduced in the treatment of both lymphoid and myeloid haematological malignancies in adults. After a general introduction on the principles of antibody selection for therapy, this review summarizes the results of the clinical trials that led to the approval of antibodies by the FDA (Food and Drug Administration, USA) and/or Read More

Monoclonal antibodies (mAbs) have become an integral part of therapeutic strategies used to treat solid tumours. Directed against membrane-bound receptors or extracellular ligands with high specificity, they target elements upstream in the signal transduction pathways that contribute to malignant growth, proliferation, survival, angiogenesis and spread. Several mAbs have now received regulatory approval - trastuzumab, Read More

Important advances have been achieved with molecular targeted agents in clinical oncology. Breast, colon, and lung cancer, are now commonly treated with a combination of chemotherapy and targeted agents. In this article the authors discuss the limitations of targeted therapy development, failures of previous studies, and possible strategies for an intelligent drug development. Initial attempts to block mTOR in Read More

Vascular disrupting agents (VDAs) represent a novel class of drugs targeting the tumor's blood supply. Conceptually and operationally different from currently used antiangiogenic agents, VDAs have a high specificity for the established but abnormal tumor vasculature. Upon administration, rapid changes in the microtubule cytoskeleton of tumor endothelial cells are induced, resulting in a cascade of events ultimately leading to blo Read More

Inducing DNA damage is a well known strategy for attacking cancer, already being used for many years by the application of a variety of anti cancer drugs. Tumor cells and other rapidly dividing cells are more sensitive to DNA damage caused by DNA damaging agents compared to normal cells. While normal cells can rely on various mechanisms for DNA repair in order to protect the integrity of the genome and to promote Read More

The enzyme poly(ADP)-ribose polymerase-1 (PARP-1) plays an important role in the repair of DNA damage via a mechanism called base excision repair (BER). Initially, inhibition of PARP-1 showed to be a promising anti-tumor strategy in preclinical models using BRCA1 and BRCA2 deficient tumor cell lines. More recently, several small molecules targeting PARP-1 entered the clinic and demonstrated compelling anti-tumor act Read More

Histone deacetylase (HDAC) inhibitors constitute a new group of epigenetic agents that has gained much attention in cancer drug development. Research in the field of epigenetics is furthering our understanding of malignant behavior and providing novel targets to improve the outcomes of cancer therapy. In this review we present an overview of the complex landscape of HDAC inhibitor development starting from a discussi Read More

Irinotecan (CPT-11) is a widely used anticancer drug, especially for the treatment of colorectal cancer. Irinotecan is considered an inactive prodrug that requires activation to the active metabolite SN-38. Patients treated with irinotecan occasionally experience severe neutropenia and delayed diarrhea, and the occurrence of these adverse reactions is unpredictable and still largely unexplained. Various studies have demonstrat Read More

After almost 20 years of research, DNA vaccination is still a relatively young technique in the vaccine-toolbox. DNA vaccines can easily be modified by conventional cloning techniques, are relatively easy to produce and might be particularly useful for therapeutic vaccination against intracellular pathogens and cancer. After the early pre-clinical successes, DNA vaccination moved into the clinic and numerous trials have been perf Read More

The taxanes are widely used in the cytotoxic treatment of many solid tumours. Their optimal scheduling, however, remains unconfirmed. Here we review the development of both paclitaxel and docetaxel to identify evidence influencing the choice of schedule. Early work with paclitaxel identified that it exhibits non-linear pharmacokinetics which has important clinical implications. Paclitaxel has been administered with a Read More