91
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      How Taxol/paclitaxel kills cancer cells

      other
      1
      Molecular Biology of the Cell
      The American Society for Cell Biology

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Taxol (generic name paclitaxel) is a microtubule-stabilizing drug that is approved by the Food and Drug Administration for the treatment of ovarian, breast, and lung cancer, as well as Kaposi's sarcoma. It is used off-label to treat gastroesophageal, endometrial, cervical, prostate, and head and neck cancers, in addition to sarcoma, lymphoma, and leukemia. Paclitaxel has long been recognized to induce mitotic arrest, which leads to cell death in a subset of the arrested population. However, recent evidence demonstrates that intratumoral concentrations of paclitaxel are too low to cause mitotic arrest and result in multipolar divisions instead. It is hoped that this insight can now be used to develop a biomarker to identify the ∼50% of patients that will benefit from paclitaxel therapy. Here I discuss the history of paclitaxel and our recently evolved understanding of its mechanism of action.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: not found

          Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore.

          In eukaryotes, chromosome segregation during cell division is facilitated by the kinetochore, a multiprotein structure that is assembled on centromeric DNA. The kinetochore attaches chromosomes to spindle microtubules, modulates the stability of these attachments and relays the microtubule-binding status to the spindle assembly checkpoint (SAC), a cell cycle surveillance pathway that delays chromosome segregation in response to unattached kinetochores. Recent studies are shaping current thinking on how each of these kinetochore-centred processes is achieved, and how their integration ensures faithful chromosome segregation, focusing on the essential roles of kinase-phosphatase signalling and the microtubule-binding KMN protein network.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint.

            Cells that cannot satisfy the spindle assembly checkpoint (SAC) are delayed in mitosis (D-mitosis), a fact that has useful clinical ramifications. However, this delay is seldom permanent, and in the presence of an active SAC most cells ultimately escape mitosis and enter the next G1 as tetraploid cells. This review defines and discusses the various factors that determine how long a cell remains in mitosis when it cannot satisfy the SAC and also discusses the cell's subsequent fate.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Apoptosis in cancer.

              In the last decade, basic cancer research has produced remarkable advances in our understanding of cancer biology and cancer genetics. Among the most important of these advances is the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. For example, it is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anticancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit.
                Bookmark

                Author and article information

                Contributors
                Role: Monitoring Editor
                Journal
                Mol Biol Cell
                Mol. Biol. Cell
                molbiolcell
                mbc
                Mol. Bio. Cell
                Molecular Biology of the Cell
                The American Society for Cell Biology
                1059-1524
                1939-4586
                15 September 2014
                : 25
                : 18
                : 2677-2681
                Affiliations
                Department of Cell and Regenerative Biology and Carbone Cancer Center, University of Wisconsin, Madison, WI 53705
                University of Wisconsin
                Author notes
                1Address correspondence to: Beth A. Weaver ( baweaver@ 123456wisc.edu ).
                Article
                E14-04-0916
                10.1091/mbc.E14-04-0916
                4161504
                25213191
                87aaec63-eaa8-46d8-9447-f2bb17bd5380
                © 2014 Weaver. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0).

                “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.

                History
                : 22 May 2014
                : 30 June 2014
                : 07 July 2014
                Categories
                MBoC Perspective on Cell Biology and Human Health

                Molecular biology
                Molecular biology

                Comments

                Comment on this article