Current Cancer Drug Targets - Volume 9, Issue 3, 2009

It was with great pleasure that I accepted the invitation to be Guest Editor for this issue of Current Cancer Drug Targets. This volume collates reviews by experts on a wide range of research topics relevant to anti-cancer drug sensitivity and resistance, considering both traditional chemotherapeutic agents and newer, targeted therapies. The use of chemotherapy to treat cancer began in 1943 following the observa Read More

Protein kinase inhibitors (PKI) are becoming key agents in modern cancer chemotherapy, and combination of PKIs with classical chemotherapeutic drugs may help to overcome currently untreatable metastatic cancers. Since chemotherapy resistance is a recurrent problem, mechanisms of resistance should be clarified in order to help further drug development. Here we suggest that in addition to PKI resistance based on alt Read More

Drug resistance is a serious limitation to the effective treatment of a number of common malignancies. Thirty years of laboratory and clinical research have greatly defined the molecular alterations underlying many drug resistance processes in cancer. Based on this knowledge, strategies to overcome the impact of resistance and increase the efficacy of cancer treatment have been translated from laboratory models to cli Read More

P-glycoprotein (Pgp), coded for by the mdr1 gene, is one of the ABC transporters held responsible for the phenomenon of multidrug resistance (mdr), which is reflected by a rapidly escalating failure of chemotherapy with different classes of cytotoxic agents: anthracyclins, vinca alkaloids, taxanes, epipodophylotoxins. Although overcoming resistance conveyed by Pgp alone may not be sufficient for reaching effective treat Read More

Over the past two decades, a number of chemical entities have been investigated in the continuing quest to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in cancer cells and some have undergone clinical trials, but currently none are in clinical use. Unfortunately, most of these agents suffer clinically from their intrinsic toxicity or from undesired effects on the pharmacokinetics of the accompanying anti-ca Read More

Resistance to chemotherapy is a major obstacle in the treatment of cancer. Despite the advent of new chemotherapies and molecular-targeted therapies, approximately 90% of patients with metastatic cancer succumb to their disease. Drug resistance, either acquired or intrinsic, often prevents tumour cells from undergoing sufficient levels of programmed cell death or apoptosis, resulting in cancer cell survival and trea Read More

Drug resistance remains a major clinical challenge for cancer treatment. One mechanism by which tumor cells develop resistance to cytotoxic agents and radiation is related to resistance to apoptosis. Apoptosis is a well-organised process of cell death pre-programmed inside the cell. Apoptosis can be initiated either by activation of death receptors on the cell surface membranes (extrinsic pathway) or through a series Read More

Bleomycin, a widely used anti-tumor agent, is well-known to cause single- and double-strand breaks in cellular DNA in vivo and in vitro leading finally to genomic instability of damaged cells. Bleomycin causes an increase of reactive oxygen species resulting in oxidative stress and pulmonary fibrosis. Further, bleomycin induces apoptosis and senescence in epithelial and non-epithelial cells of the lung. Caveolin-1 is a scaffold pr Read More

A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel [1]. Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the i Read More

Anthracyclines are an important reagent in many chemotherapy regimes for treating a wide range of tumors. One of the primary mechanisms of anthracycline action involves DNA damage caused by inhibition of topoisomerase II. Enzymatic detoxification of anthracycline is a major critical factor that determines anthracycline resistance. Natural product, daunorubicin a toxic analogue of anthracycline is reduced to less toxic Read More

When treating cancer, cytotoxic agents are intended to exert their effect on rapidly proliferating cancer cells. However, often cancer chemotherapies lack specificity which can lead to toxicity and undesirable side affects. Many approaches have been designed to target tumors. Selective chemotherapies can be established by focusing on distinctive physiological, morphological and environmental differences betw Read More

Despite major improvements in the surgical management the prognosis for patients bearing malignant gliomas is still dismal. Malignant gliomas are notoriously resistant to treatment and the survival time of patients is between 3-8 years for low-grade and anaplastic gliomas and 6 - 12 month for glioblastoma. Increasing malignancy of gliomas correlates with an increase in cellularity and a poorly organized tumor vasculature leadi Read More

Melanoma is the most aggressive form of skin cancer and advanced stages are inevitably resistant to conventional therapeutic agents. In particular, the inability of undergo apoptosis in response to chemotherapy and other external stimuli poses a selective advantage for tumor progression, metastasis formation as well as resistance to therapy in melanoma. Herein, we will review the molecular mechanisms of se Read More

Breast cancer is the second leading cause of cancer deaths. This disease is estimated to be diagnosed in over one million people worldwide and to cause more than 400,000 deaths each year. This is a significant health problem in terms of both morbidity and mortality. Chemotherapy forms part of a successful treatment regime in many cases; however, as few as half of the patients treated may benefit from this, as a result of intr Read More

Amplification of the HER-2 gene occurs in approximately 25% of breast cancers, causing up-regulation of key signaling pathways which control cell growth and survival. In breast cancer patients, HER-2 overexpression correlates with an aggressive phenotype and poor prognosis. HER-2, therefore, has become the focus of many anti-cancer therapeutic approaches. Trastuzumab (Herceptin™), a humanized monoclonal ant Read More

The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin-pathway (PI3K/AKT/mTOR-pathway) plays a role in the regulation of cell proliferation, cell survival, angiogenesis and resistance to anti-tumor treatments. In many tumor types the PI3K/AKT/mTOR-pathway is found activated through several different underlying mechanisms. Since this pathway is believed to largely drive the maligna Read More