Current Pharmaceutical Biotechnology - Volume 13, Issue 9, 2012

Natural compounds represent a significant source for the development of novel medicines. Finding the target proteins for a natural compound is the most important step towards understanding its molecular mechanism for therapeutic usage. In fact, the search for target proteins could be considered the first step of the drug discovery and development pipeline. While experimental determination of compound-protein intera Read More

The highly polymorphic human cytochrome P450 2D6 (CYP2D6) metabolizes about 25% of currently used drugs. In this study, we have explored the interaction of a large number of substrates (n = 120) with wild-type and mutated CYP2D6 by molecular docking using the CDOCKER module. Before we conducted the molecular docking and virtual mutations, the pharmacophore and QSAR models of CYP2D6 substrates were develope Read More

Concomitant consumption of grapefruit juice (GFJ) causes increases in the plasma concentration of a variety of drugs due to inhibition of intestinal CYP3A enzyme. Dihydropyridine calcium channel blockers belong to the category of drugs that are most prone to undergo such interaction. Increases in area under the plasma concentration-time curve (AUC) due to GFJ differ greatly depending on the dihydropyridine administ Read More

Herbal supplements are often used concomitantly with conventional medications resulting in considerable potential for herb-drug interactions. These interactions, which are generally through interfering with pharmacokinetic and/or pharmacodynamic pathways, may result in beneficial effects or more often adverse reactions such as toxicity or treatment failure and may be influenced by multiple environmental and/or g Read More

Attenuated measles virus vaccine strains have emerged as a promising oncolytic vector platform, having shown significant anti-tumor activity against a broad range of malignant neoplasms. Measles virus strains derived from the attenuated Edmonston-B (MV-Edm) vaccine lineage have been shown to selectively infect, replicate in and lyse cancer cells while causing minimal cytopathic effect on normal tissues. This review Read More

Viruses function in close harmony with the signaling machinery of their host. Upon exposure to the cell, a battery of viral products become engaged in boosting friendly signaling elements of the host or suppressing harmful ones. The efficiency of viral replication is indeed the biological outcome of this interaction between cellular and host signaling molecules. Oncolytic viruses, natural or man-made, follow the same set of rules of e Read More

Oncolytic virotherapy is an evolving but, as yet, unrealized treatment option for cancer. This approach harnesses the cancer-restricted replicative activity of engineered viruses to achieve tumor cell kill. Tumors that are resistant to chemotherapy or radiotherapy can be susceptible to viral oncolysis because of distinct cell kill mechanisms. There is now compelling evidence that collateral induction of anti-tumor immune resp Read More

Cancer Targeting Gene-Viro-Therapy (CTGVT) and Gene Armed Oncolytic Virus Therapy (GAOVT) both are identical by inserting an antitumor gene into an oncolytic virus. This approach has gradually become a hot topic in cancer therapy, because that CTGVT (GAOVT) has much higher antitumor than that of either gene therapy alone or oncolytic virotherapy alone. We proposed the CTGVT strategy in 1999-2001, insisted Read More

Oncolytic viruses (OVs) are designed to replicate in, and subsequently lyse cancer cells. Numerous oncolytic virus platforms are currently in development. Here we review preclinical and clinical experience with JX-594, the lead candidate from the targeted and armed oncolytic poxvirus class. JX-594 is derived from a vaccinia vaccine strain that has been engineered for 1) enhanced cancer targeting and 2) has been “arm Read More

The recent FDA approval of Sipuleucel-T for the treatment of prostate cancer represents an important milestone of cancer immunotherapy, which, for the first time, validates the concept of bringing true clinical benefit to cancer patients by stimulating patients’ own anti-tumor immunity. Among the different experimental cancer immunotherapies, oncolytic virotherapy may represent a low-cost yet potent and personalized cancer Read More

Herpes simplex virus (HSV) is a well-known vector that is often used for gene therapy to treat cancers. The most attractive feature of HSV is its ability to destroy tumors through a distinctive oncolytic mechanism where the virus can destroy cancer cells via cell lysis, a killing function that no anti-cancer drugs can mimic. Importantly, HSV is a safe and effective virus that can be easily manipulated to preferentially replicate in t Read More

Herpes simplex viruses (HSVs) have entered clinical trials as oncolytic agents. The following properties make them good candidates. It is a mild pathogen; drugs (Aciclovir) are available to control viral infection; the large genome is amenable to genetic engineering, they can be rendered cancer-specific by deletion of genes, envelope glycoproteins allow the insertion of heterologous ligands to achieve modification of the n Read More

Adenoviruses (Ads) are arguably one of the most potent viruses for in vivo gene therapy, vaccine, and oncolytic applications. The attraction for the use of Ads stems from their ability to infect a wide range of dividing and non-dividing cell types in some cases to efficiencies of nearly 100%. Additional benefits include their stability, the ability to purify the vector to concentrations of up to 1013 particles/ml, and the fact that vir Read More

Replication-selective tumor-specific viruses present a novel approach for treatment of neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity correlates closely with human telomerase reverse transcriptase ( Read More

Single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. The combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. The first combination treatments exploited for cancer therapy involved the use of several cytoto Read More

There has been interest in using viruses to treat cancer for over a century. Recent clinical efforts, driven on by significant preclinical advances, have focussed on the safety of using replication-competent viruses. Recently published clinical trials of six oncolytic viruses (adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus and vaccinia) have added to the accumulating data that endorse oncolytic viruses as Read More

Oncolytic virotherapy with mutants derived from Herpes simplex virus (HSV) type 1 exhibit significant antitumor effects in preclinical models. Several mutants have now been tested in clinical trials for a variety of cancer types, and all have been found to be safe. While there have been hints of antitumor efficacy with prolonged survival in some cases compared with historical controls, dramatic responses have been elusi Read More

The oncolytic virus, being a promising new therapeutic strategy for cancer, has inspired a wave of recent clinical research and development in China. The first commercialized oncolytic virus, Oncorine, was approved by Chinese SFDA in November 2005 for nasopharyngeal carcinoma combined with chemotherapy. Since then, a number of oncolytic viruses have been moved into clinical trials. Among these are the arme Read More