Antitumour effects of taxanes with particular emphasis on their use in the treatment of melanoma
More details
Hide details
Katedra i Zakład Patofizjologii, Uniwersytet Medyczny w Lublinie, Polska
Paula Wróblewska-Łuczka   

Katedra i Zakład Patofizjologii, Uniwersytet Medyczny w Lublinie, Jaczewskiego 8b, 20-090, Lublin, Polska
Med Srod. 2020;23(1-4):9–17
Introduction and objective:
Cancer is diagnosed in millions of people worldwide, and their number is constantly growing. For many years researchers have made efforts to find more effective drugs in order to control this deadly disease. These compounds include taxanes – substances derived from yew extract which exhibit anti-cancer properties.

Brief description of the state of knowledge:
Taxanes include paclitaxel, docetaxel, and cabazitaxel. These are cytostatic drugs that act by stabilizing tubulin. There are two theories to explain cell death after the application of taxanes: one of which is cell arrest in mitosis, and the other is death by activation of checkpoints in response to abnormal chromosome segregation among cells that have undergone abnormal mitosis or mitotic slippage. Death occurs through the mechanism of apoptosis. Scientists are developing various ways to increase the bioavailability of drugs to achieve better therapeutic effects, and to use the drug in the lowest possible dose to minimize the risk of side effects. Taxanes are commonly used in the treatment of many types of cancer, for example, in the treatment of patients with breast cancer, ovarian cancer, prostate or stomach cancer and non-small cell lung cancer. The article discusses these therapies, taking into account the latest scientific reports. In addition, the possibility of treating the most dangerous skin cancer – melanoma has been described in detail, in which these drugs have not yet been routinely used.

Scientific studies develop knowledge concerning the effect of taxanes and confirm their anti-cancer properties, which save the lives of an increasingly larger group of cancer patients.

Mattiuzzi C, Lippi G. Current Cancer Epidemiology. J Epidemiol Glob Health. 2019; 9(4): 217–222. doi: 10.2991/jegh.k.191008.001.
2. dostęp z dnia 04.03.2021.
Wang XS, Zhang L, Li X, et al. Nanoformulated paclitaxel and AZD9291 synergistically eradicate non-small-cell lung cancers in vivo. Nanomedicine (Lond). 2018; 13(10): 1107–1120. doi: 10.2217/nnm-2017-0355.
Schadendorf D, van Akkooi ACJ, Berking C, et al. Melanoma. Lancet. 2018; 392(10151): 971–984. doi: 10.1016/S0140-6736(18)31559-9.
Ovejero S, Bueno A, Sacristán MP. Working on Genomic Stability: From the S-Phase to Mitosis. Genes (Basel). 2020; 11(2): 225. doi: 10.3390/genes11020225.
Hume S, Dianov GL, Ramadan K. A unified model for the G1/S cell cycle transition. Nucleic Acids Res. 2020; 48(22): 12483–12501. doi: 10.1093/nar/gkaa1002.
Sinha D, Duijf PHG, Khanna KK. Mitotic slippage: an old tale with a new twist. Cell Cycle. 2019; 18(1): 7–15. doi: 10.1080/15384101.2018.1559557.
Glover TW, Wilson TE, Arlt MF. Fragile sites in cancer: more than meets the eye. Nat Rev Cancer. 2017; 17(8): 489–501. doi: 10.1038/nrc.2017.52.
Kentsis A. Why do young people get cancer?. Pediatr Blood Cancer. 2020; 67(7): e28335. doi: 10.1002/pbc.28335.
Serkova NJ, Eckhardt SG. Metabolic Imaging to Assess Treatment Response to Cytotoxic and Cytostatic Agents. Front Oncol. 2016; 6: 152. doi: 10.3389/fonc.2016.00152.
Weaver BA. How Taxol/paclitaxel kills cancer cells. Mol Biol Cell. 2014; 25(18): 2677–2681. doi: 10.1091/mbc.E14-04-0916.
Ibrahim EY, Ehrlich BE. Prevention of chemotherapy-induced peripheral neuropathy: A review of recent findings. Crit Rev Oncol Hematol. 2020; 145: 102831. doi: 10.1016/j.critrevonc.2019.102831.
Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett. 2019; 24: 40. doi: 10.1186/s11658-0190164-y.
Zhang D, Yang R, Wang S, Dong Z. Paclitaxel: new uses for an old drug. Drug Des Devel Ther. 2014; 8: 279–284. doi: 10.2147/DDDT.S56801.
Zaiyou J, Li M, Xiqiao H. An endophytic fungus efficiently pro ducing paclitaxel isolated from Taxus wallichiana var. mairei. Medicine (Bal-timore). 2017; 96(27): e7406. doi: 10.1097/MD.0000000000007406.
Abu Samaan TM, Samec M, Liskova A, Kubatka P, Büsselberg D. Paclitaxel's Mechanistic and Clinical Effects on Breast Cancer. Biomo -lecules. 2019; 9(12): 789. doi: 10.3390/biom9120789.
Roman JA, Reucroft I, Martin RA, Hurtado A, Mao HQ. Local Release of Paclitaxel from Aligned, Electrospun Microfibers Promotes Axonal Extension. Adv Healthc Mater. 2016; 5(20): 2628–2635. doi: 10.1002/adhm.201600415.
Goodson HV, Jonasson EM. Microtubules and Microtubule-Associated Proteins. Cold Spring Harb Perspect Biol. 2018; 10(6): a022608. doi: 10.1101/cshperspect.a022608.
McIntosh JR. Mitosis. Cold Spring Harb Perspect Biol. 2016; 8(9): a023218. doi: 10.1101/cshperspect.a023218.
Field JJ, Díaz JF, Miller JH. The binding sites of microtubule-stabilizing agents. Chem Biol. 2013; 20(3): 301–15. doi: 10.1016/j.chembiol.2013.01.014.
Yang CH, Horwitz SB. Taxol®: The First Microtubule Stabilizing Agent. Int J Mol Sci. 2017; 18(8): 1733. doi: 10.3390/ijms18081733.
Mikuła-Pietrasik J, Witucka A, Pakuła M, et al. Comprehensive review on how platinum- and taxane-based chemotherapy of ovarian cancer affects biology of normal cells. Cell Mol Life Sci. 2019; 76(4): 681–697. doi: 10.1007/s00018-018-2954-1.
Ruan W, Lim HH, Surana U. Mapping Mitotic Death: Functional Integration of Mitochondria, Spindle Assembly Checkpoint and Apoptosis. Front Cell Dev Biol. 2019; 6: 177. doi: 10.3389/fcell.2018.00177.
Nakayama Y, Inoue T. Antiproliferative Fate of the Tetraploid Formed after Mitotic Slippage and Its Promotion; A Novel Target for Cancer Therapy Based on Microtubule Poisons. Molecules. 2016; 21(5): 663. doi: 10.3390/molecules21050663.
Bates D, Eastman A. Microtubule destabilising agents: far more than just antimitotic anticancer drugs. Br J Clin Pharmacol. 2017; 83(2): 255–268. doi: 10.1111/bcp.13126.
Koh SB, Mascalchi P, Rodriguez E, Lin Y, Jodrell DI, Richards FM, Lyons SK. A quantitative FastFUCCI assay defines cell cycle dynamics at a single-cell level. J Cell Sci. 2017; 130(2): 512–520. doi: 10.1242/jcs.195164.
Yasuhira S, Shibazaki M, Nishiya M, Maesawa C. Paclitaxel-induced aberrant mitosis and mitotic slippage efficiently lead to proliferative death irrespective of canonical apoptosis and p53. Cell Cycle. 2016; 15(23): 3268–3277. doi: 10.1080/15384101.2016.1242537.
van Eerden RAG, Mathijssen RHJ, Koolen SLW. Recent Clinical Developments of Nanomediated Drug Delivery Systems of Taxanes for the Treatment of Cancer. Int J Nanomedicine. 2020; 15: 8151–8166. doi: 10.2147/IJN.S272529.
Kopeckova K, Eckschlager T, Sirc J, Hobzova R, Plch J, Hrabeta J, Michalek J. Nanodrugs used in cancer therapy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019; 163(2): 122–131. doi: 10.5507/bp.2019.010.
Kommineni N, Mahira S, Domb AJ, Khan W. Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects. Pharmaceutics. 2019; 11(3): 141. doi: 10.3390/pharmaceutics11030141.
Lee H, Park S, Kang JE, Lee HM, Kim SA, Rhie SJ. Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with solvent-based taxanes for metastatic breast cancer: A meta-analysis. Sci Rep. 2020; 10(1): 530. doi: 10.1038/s41598-019-57380-0.
Kang BW, Kwon OK, Chung HY, Yu W, Kim JG. Taxanes in the Treatment of Advanced Gastric Cancer. Molecules. 2016; 21(5): 651. doi: 10.3390/molecules21050651.
Willson ML, Burke L, Ferguson T, Ghersi D, Nowak AK, Wilcken N. Taxanes for adjuvant treatment of early breast cancer. Cochrane Database Syst Rev. 2019; 9(9): CD004421. doi: 10.1002/14651858.CD004421.pub3.
Ter Welle-Butalid MEE, Vriens IJHI, Derhaag JGJ, Leter EME, de Die-Smulders CEC, Smidt MM, van Golde RJTR, Tjan-Heijnen VCGV. Counseling young women with early breast cancer on fertility preser vation. J Assist Reprod Genet. 2019; 36(12): 2593–2604. doi: 10.1007/s10815-019-01615-6.
Bai S, Zhang BY, Dong Y. Impact of taxanes on androgen receptor signaling. Asian J Androl. 2019; 21(3): 249–252. doi: 10.4103/aja.aja_37_18.
Murat Sedef A, Taner Sumbul FKA, Ayberk Besen A, Hacioglu B, Gunaldi M, Nayir E, Tanriverdi O, Arpaci E, Abali H, Ozyilkan O. Addition of taxanes to combination chemotherapy in distal intestinal gastric cancer is more beneficial than proximal ones: A multicenter retrospective study of Turkish Oncology Group. J BUON. 2019; 24(2): 650–655.
Kumarasamy V, Ruiz A, Nambiar R, Witkiewicz AK, Knudsen ES. Chemotherapy impacts on the cellular response to CDK4/6 inhibition: distinct mechanisms of interaction and efficacy in models of pancreatic cancer. Oncogene. 2020; 39(9): 1831–1845. doi: 10.1038/s41388-019-1102-1.
Pignata S, Pisano C, Di Napoli M, Cecere SC, Tambaro R, Attademo L. Treatment of recurrent epithelial ovarian cancer. Cancer. 2019; 125(24): 4609–4615. doi: 10.1002/cncr.32500. Erratum in: Cancer. 2020; 126(7): 1588.
Thomas M, Spigel DR, Jotte RM, et al. nab-paclitaxel/carboplatin in -duction in squamous NSCLC: longitudinal quality of life while on chemotherapy. Lung Cancer (Auckl). 2017; 8: 207–216. doi: 10.2147/LCTT.S138570.
Thomas M, Spigel DR, Jotte RM, et al. nab-paclitaxel/carboplatin in -duction in squamous NSCLC: longitudinal quality of life while on chemotherapy. Lung Cancer (Auckl). 2017; 8: 207–216.
Cao X, Tan T, Zhu D, et al. Paclitaxel-Loaded Macrophage Membrane Camouflaged Albumin Nanoparticles for Targeted Cancer Therapy. Int J Nanomedicine. 2020; 15: 1915–1928. doi: 10.2147/IJN.S244849.
Clemente N, Argenziano M, Gigliotti CL, et al. Paclitaxel-Loaded Nanosponges Inhibit Growth and Angiogenesis in Melanoma Cell Models. Front Pharmacol. 2019; 10: 776. doi: 10.3389/fphar.2019.00776.
Su Y, Hu J, Huang Z, et al. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance. Drug Des Devel Ther. 2017; 11: 659–668. doi: 10.2147/DDDT.S127328.
Wanderley CW, Colón DF, Luiz JPM, Oliveira FF, Viacava PR, Leite CA, Pereira JA, Silva CM, Silva CR, Silva RL, Speck-Hernandez CA, Mota JM, Alves-Filho JC, Lima-Junior RC, Cunha TM, Cunha FQ. Pac-litaxel Reduces Tumor Growth by Reprogramming Tumor-Associated Macrophages to an M1 Profile in a TLR4-Dependent Manner. Cancer Res. 2018; 78(20): 5891–5900. doi: 10.1158/0008-5472.CAN-17-3480.
Bhatty M, Kato S, Piha-Paul SA, et al. Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies. Cancer. 2019; 125(3): 463–472. doi: 10.1002/cncr.31812.
Chen S, Zhang X, Shen L, Qi H, Ma W, Cao F, Xie L, Song Z, Wu Y, Li D, Wen X, Fan W. Transcatheter arterial infusion of anti-programmed cell death 1 antibody pembrolizumab combined with temozolomide or nab-paclitaxel in patient with primary anorectal malignant melanoma: Four case reports. J Cancer Res Ther. 2020; 16(2): 387–392. doi: 10.4103/jcrt.JCRT_75_20.
Flaherty KT, Lee SJ, Zhao F, et al. Phase III trial of carboplatin and paclitaxel with or without sorafenib in metastatic melanoma. J Clin Oncol. 2013; 31(3): 373–379. doi: 10.1200/JCO.2012.42.1529.
Jamal R, Lapointe R, Cocolakis E, et al. Peripheral and local predictive immune signatures identified in a phase II trial of ipilimumab with carboplatin/paclitaxel in unresectable stage III or stage IV melanoma. J Immunother Cancer. 2017; 5(1): 83. doi: 10.1186/s40425-017-0290-x.
Fruehauf JP, El-Masry M, Osann K, Parmakhtiar B, Yamamoto M, Jakowatz JG. Phase II study of pazopanib in combination with paclitaxel in patients with metastatic melanoma. Cancer Chemother Pharmacol. 2018; 82(2): 353–360. doi: 10.1007/s00280-018-3624-6.
Reddy TL, Garikapati KR, Reddy SG, et al. Simultaneous delivery of Paclitaxel and Bcl-2 siRNA via pH-Sensitive liposomal nanocarrier for the synergistic treatment of melanoma. Sci Rep. 2016; 6: 35223. doi: 10.1038/srep35223.
Ko G, Kim T, Ko E, Park D, Lee Y. Synergistic Enhancement of Pacli-taxel-induced Inhibition of Cell Growth by Metformin in Melanoma Cells. Dev Reprod. 2019; 23(2): 119–128. doi: 10.12717/DR.2019.23.2.119.
Vera-Aguilera J, Bedikian AY, Bassett RL, et al. Phase I/II Study of Hepatic Arterial Infusion of Nab-paclitaxel in Patients With Metastatic Melanoma to the Liver. Am J Clin Oncol. 2018; 41(11): 1132–1136. doi: 10.1097/COC.0000000000000436.
McQuade JL, Posada LP, Lecagoonporn S, et al. A phase I study of TPI 287 in combination with temozolomide for patients with meta-static melanoma. Melanoma Res. 2016; 26(6): 604–608. doi: 10.1097/CMR.0000000000000296.