PURPOSE To explore the association between progression-free survival and overall survival time in patients with castration-resistant prostate cancer treated with microtubule-targeted therapies. EXPERIMENTAL DESIGN We retrospectively studied patients treated in three trials evaluating a taxane or an epothilone for progressive castration-resistant prostate cancer. Study subjects were 98 patient...

In our increasingly sophisticated world, it is remarkable how, even today, most decisions on combination chemotherapy regimens are still made on purely empirical grounds. Whereas several strategies have been pursued, the most common approach is to combine agents based on their single-agent activity and toxicity profile. Thus, if drug A has 20% activity in disease X as a single agent, and drug B...

Several studies have demonstrated the therapeutic potential of applying microtubule- (MT-) stabilizing agents (MSAs) that cross the blood-brain barrier to promote axon regeneration and prevent axonal dystrophy in rodent models of spinal cord injury and neurodegenerative diseases. Paradoxically, administration of MSAs, which have been widely prescribed to treat malignancies, is well known to cau...

Some of the most therapeutically interesting natural products are mixed polyketide/nonribosomal peptide molecules, including bleomycin and epothilones (anticancer agents) and FK506 and rapamycin (immunosuppressive drugs).1-3 These enzymatically assembled molecules are encoded by multimodular protein arrays that, through their chain-ordering, determine the structure of the natural product elonga...

BACKGROUND Ixabepilone (BMS-247550), an epothilone B analog, is a microtubule stabilizing agent which has shown activity in several different tumor types and preclinical models in melanoma. In an open label, one-arm, multi-center phase II trial the efficacy and toxicity of this epothilone was investigated in two different cohorts: chemotherapy-naïve (previously untreated) and previously treated...

Disorazoles are macrocyclic polyketides first isolated from the fermentation broth of the myxobacterium Sorangium cellulosum. Both the major fermentation product disorazole A1 and its much rarer companion disorazole C1 exhibit potent cytotoxic activity against many human tumor cells. Furthermore, the disorazoles appear to bind tubulin uniquely among known antimitotic agents, promoting apoptosis...

In this study, we investigated the in vitro and in vivo efficacy of patupilone (epothilone B, EPO906), a novel nontaxane microtubule stabilizing agent, in treatment of multiple myeloma (MM). Patupilone directly inhibited growth and survival of MM cells, including those resistant to conventional chemotherapies, such as the taxane paclitaxel. Patupilone induced G2M arrest of MM cells, with subseq...

PURPOSE Ixabepilone is an epothilone B analog that binds to microtubules and results in microtubule stabilization and mitotic arrest. Ixabepilone was evaluated for efficacy and safety in a phase II clinical trial for women with metastatic breast cancer. PATIENTS AND METHODS Patients were eligible if they had not previously received treatment with a taxane and had measurable metastatic breast ...

Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellular resistance to the class of MIAs known as microtubule-stabilizing agents (MSA). The human lung canc...

BACKGROUND Many previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and thera...