Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Dec 2008
ReviewPreclinical discovery of ixabepilone, a highly active antineoplastic agent.
The epothilones and their analogs constitute a novel class of antineoplastic agents, produced by the myxobacterium Sorangium cellulosum. These antimicrotubule agents act in a similar manner to taxanes, stabilizing microtubules and resulting in arrested tumor cell division and apoptosis. Unlike taxanes, however, epothilones and their analogs are macrolide antibiotics, with a distinct tubulin binding mode and reduced susceptibility to a range of common tumor resistance mechanisms that limit the effectiveness of taxanes and anthracyclines. ⋯ Ixabepilone has shown promising phase II clinical efficacy and acceptable tolerability in a wide range of cancers, including heavily pretreated and drug-resistant tumors. Based on these results, a randomized phase III trial was conducted in anthracycline-pretreated or resistant and taxane-resistant metastatic breast cancer to evaluate ixabepilone in combination with capecitabine. Ixabepilone combination therapy showed significantly superior progression-free survival and tumor responses over capecitabine alone.
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Cancer Chemother. Pharmacol. · Dec 2008
Comparative StudySynergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.
Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. ⋯ These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.
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Cancer Chemother. Pharmacol. · Dec 2008
Antitumor activity of noscapine in human non-small cell lung cancer xenograft model.
An antitussive plant alkaloid, Noscapine HCl (Nos) displays anticancer activity and has a safe pharmacological profile in humans. The current study was aimed to investigate the in vitro and in vivo anti tumor activity of Nos to determine possible mechanisms of anti tumor activity for treatment of non-small cell lung cancer (NSCLC). ⋯ Our studies suggest that potent antitumor activity of Nos against NSCLC cells. Oral administration of Nos showed significant reduction in tumor volume in human non-small cell lung tumor xenograft in nude mice in a dose dependant manner. Thus, Nos is a promising novel chemotherapeutic agent for the treatment of human lung cancer.