Paclitaxel

Brand Name: Taxol, Abraxane

Paclitaxel is used to treat ovarian carcinoma, breast carcinoma, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma.1 Abraxane (albumin-bound paclitaxel) is used to treat metastatic breast cancer, locally advanced or metastatic non-small cell lung cancer, and metastatic adenocarcinoma of the pancreas.2

How Does Paclitaxel Work?

Microtubule.

Microtubules are structural polymers that are part of the "skeleton" of the cell. They play essential roles in cell shape, motility, and division.3

Microtubule assembly (lengthening) and disassembly (shortening).

Microtubules are able to rapidly assemble and disassemble to perform various functions. This behavior, termed dynamic instability, is closely linked to the state and context of the cell.3

Partial stages of mitosis in sequence. From left to right: a cell with microtubules attached to DNA; a cell with DNA getting pulled toward opposite sides of the cell; and a cell with evenly split DNA in opposite sides of the cell.

For example, mitosis is a process in which a cell evenly splits DNA into two new nuclei prior to cell division. Microtubules achieve this by attaching to DNA and pulling them apart toward opposite sides of the cell. In particular, this "pulling" force results from the shortening of microtubules through their disassembly.4

Paclitaxel binding to microtubules and inhibiting their disassembly.

Paclitaxel is a taxane drug that binds to the inner surface of microtubules and inhibits their disassembly.5,6

Paclitaxel inhibiting mitosis.

As a result, paclitaxel prevents mitosis from progressing properly. Because cancer cells rely on uncontrolled mitosis and cell division to grow, paclitaxel treatment is particularly effective at stopping cancer progression.7 However, there is still a debate on whether or not this is a physiologically relevant mechanism of how paclitaxel kills cancer cells in the body.8

On the left, paclitaxel-treated cancer cells releasing DAMPs toward immune cell. On the right, paclitaxel-treated immune cell releasing toxins toward cancer cells.

Recent studies reveal additional mechanisms of paclitaxel's anti-cancer effect: (1) cancer cells killed through paclitaxel treatment release damage-associated molecular patterns (DAMPs) that can stimulate immune cells to attack other cancer cells9; and (2) paclitaxel directly stimulates certain immune cells to release toxins that can kill cancer cells.10

Side Effects of Paclitaxel

* Severity data unavailable
Side effects profile is adapted from a study of single-agent paclitaxel as a treatment for solid tumors.1

References

1. TAXOL - Label. U.S. Food and Drug Administration (2010).

2. ABRAXANE - Label. U.S. Food and Drug Administration (2020).

3. Nogales, E. Structural Insights into Microtubule Function. Annual Review of Biochemistry 69, 277-302 (2000).

4. Mitchison, T. J. & Salmon, E. D. Poleward kinetochore fiber movement occurs during both metaphase and anaphase-A in newt lung cell mitosis. Journal of Cell Biology 119, 569-582 (1992).

5. Schiff, P. B., Fant, J. & Horwitz, S. B. Promotion of microtubule assembly in vitro by taxol. Nature 277, 665-667 (1979).

6. Nogales, E., Whittaker, M., Milligan, R. A. & Downing, K. H. High-Resolution Model of the Microtubule. Cell 96, 79-88 (1999).

7. Schiff, P. B. & Horwitz, S. B. Taxol stabilizes microtubules in mouse fibroblast cells. Proceedings of the National Academy of Sciences of the United States of America 77, 1561-1565 (1980).

8. Janssen, A., Beerling, E., Medema, R. & van Rheenen, J. Intravital FRET Imaging of Tumor Cell Viability and Mitosis during Chemotherapy. PLoS ONE 8, e64029 (2013).

9. Lau, T. S. et al. Paclitaxel Induces Immunogenic Cell Death in Ovarian Cancer via TLR4/IKK2/SNARE-Dependent Exocytosis. Cancer Immunology Research 8, 1099-1111 (2020).

10. Vennin, C. et al. Taxanes trigger cancer cell killing in vivo by inducing non-canonical T cell cytotoxicity. Cancer Cell 41, 1170-1185 (2023).