Taxol: An Anticancer Drug
Taxol (Paclitaxel) is a compound originally isolated from the
bark of the Pacific yew tree (Taxus brevifolia). It has been
approved by the U.S. Food and Drug Administration (FDA) to treat breast,
ovarian, and lung cancers as well as AIDS-related Kaposi's sarcoma.
The Mechanism of Action
Taxol hinders the growth of cancer cells by
affecting cell structures called microtubules, which play an important
role in cell functions. In normal cell growth, microtubules are
formed when a cell starts dividing. Once the cell stops dividing, the
microtubules are broken down or destroyed. Taxol
stops the microtubules from breaking down, whereby cancer
cells become clogged with microtubules and stop dividing.
In 1989, Taxol was found effective on advanced ovarian cancer.
Tumors shrank or disappeared in 30 percent of patients.
The responses to Taxol were, however, not permanent,
lasting for an average of 5 months with some up to 9 months.
In 1992, FDA approved the use of Taxol for ovarian cancer that was
resistant to treatment.
Later, Taxol was also shown effective on advanced breast cancer.
In 1994, FDA approved Taxol for treating breast cancers that recurred
or metastasized and had not responded to combination chemotherapy.
In 1998, Taxol was approved for first-line therapy for the treatment of
ovarian cancer in combination with cisplatin.
In the same year, the FDA approved Taxol, in combination with other
anticancer drugs, to treat common forms of advanced lung cancer.
The potential value of Taxol as a treatment for lymphomas,
stomach, head and neck, and bladder cancers has been studied as well.
In a clinical trial, Taxol significantly
increased survival rate and quality of life for metastatic breast
The single-agent Taxol was compared to a standard combination of
cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP),
and demonstrated almost doubled chance of survival after two years.
On the negative side, Taxol can suppress bone marrow functions,
as most other cancer drugs do.
However, the benefits for many patients with
advanced cancer often outweigh the risks associated with this drug.
dEpoB: Another Drug Working on Microtubules
The epothilones are naturally occurring, cytotoxic macrolides that
also arrest cell division and cause cell death by interfering with
microtubules, but this class of molecules
are structurally dissimilar to Taxol.
The epothilones are more potent and can fight
against Taxol-resistant cancer cell lines.
In one study (ref. 3),
the epothilone analogue, dEpoB, achieved curative effects on several
cancers including breast, lung, colon cancers, and leukemias
in nude mice experiments.
This new drug shows promise in fighting refractory cancers.
Chou, T.C., et al. 1998.
Desoxyepothilone B is curative against human tumor
xenografts that are refractory to paclitaxel.
Proc. Natl. Acad. Sci. U. S. A. 95(26):15798-802.