Epothilones

Initially discovered in the myxobacterium Sorangium cellulosum, epothilones are under evaluation as taxane alternatives. The epothilones have a similar but not identical mechanism of action to the taxanes - they are microtubule de-polymerization inhibitors - but remain effective against a variety of paclitaxel-resistant cancers and appear to have lower toxicity (E.g., Goodin et al. 2004). Epothilones are delivered in Cremophor and non-Cremophor vehicles and may cause significant neuropathy (Pronzato 2008). Epothilones have demonstrated effectiveness against ovarian, prostate, breast, colon, stomach, and kidney cancers (Goodin 2008). Ironically, the development of the epothilones, first isolated in the early 1980s, was delayed nearly as long as that of paclitaxel, in part because compounds derived from nature require a longer time to identify, to understand in terms of mechanism, and to develop the complex production processes required to go from natural compound to effective quantities of drug. The development of epothilones languished partly because of industry fascination with targeted biologics like herceptin (biologics[1] are a class of cancer treatment that uses the patient's own immune system to fight cancer), and partly because the legal windows for securing necessary property rights are not well-aligned with the lengthy research needed to develop therapeutic agents from natural compounds (Mulzer et al. 2009).

Larotaxel

A semi-synthetic compound derived from the needles of yew trees, larotaxel is closer to docetaxel than paclitaxel. It acts by stabilizing microtubules, leading to cell death through apoptosis. In early clinical trials it has shown activity against paclitaxel-resistent and non-resistant cancers, and the ability to cross the blood-brain barrier, making it a potential therapy for brain metastases (Morris and Fornier 2009). Larotaxel is being evaluated for effectiveness against non-small cell lung cancer, and breast, pancreatic, and bladder cancers.

Footnote:

1. Biologics or biological therapy: Also called biotherapy, immunotherapy, or biological response modifier therapy, biologics are a class of cancer treatment that uses the patient's own immune system to fight cancer.  Biological therapies boost or manipulate the immune system into fighting cancer in several ways: (1) by tagging cancer cells with proteins called antibodies, which identify the cancer cells as invaders to be destroyed by the immune system; (2) by boosting the effectiveness of the immune system's killer cells, (3) by stopping or slowing the process by which abnormal cells become cancer cells, or (4) by enhancing cellular repair mechanisms that prevent damaged cells from becoming abnormal or cancerous.  Because biologic therapy is more targeted, the side effects are often less severe than those caused by traditional, broadly toxic chemotherapies.

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