Terapia zmiennym polem elektrycznym (TTF) – biofizyka komórki nowotworowej jako nowy punkt zaczepienia dla terapii onkologicznej
Słowa kluczowe:
pola do leczenia nowotworów, międzybłoniak opłucnej, glejak wielopostaciowy, onkologiaStreszczenie
Elektromagnetyczne pola terapeutyczne (ang. tumor-treating fields TTF), a właściwie zmienne, niejonizujące pole elektromagnetyczne stanowi zupełnie nowe podejście w terapii nowotworowej, pozwalające na wykorzystanie zmiennych właściwości biofizycznych komórek, w celu selektywnej i skutecznej interferencji procesów mitotycznych oraz metabolicznych zachodzących w obrębie szybko dzielących się komórek nowotworowych. Poprzez zablokowanie procesów formowania się dipolarnych struktur tubiliny w wrzeciono podziałowe, terapia TTF posiada działanie antymitotyczne, które z czasem, dzięki licznym badaniom stało się tylko jednym z wielu efektów biologicznych wywoływanych przez zmienne pole elektromagnetyczne. Mnogość właściwości i ich selektywność wobec komórek nowotworowych, przełożyły się na skuteczność oraz bezpieczeństwo terapii TTF, która stała się czwartą opcją terapeutyczną dla pacjentów z glejakiem wielopostaciowym oraz złośliwym międzybłoniakiem opłucnej. Niska toksyczność terapii TTF przekłada się na jej bezpieczeństwo w skojarzeniu z pozostałymi opcjami terapeutycznymi w dziedzinie onkologii, co stwarza nowe możliwości jej szerokiego zastosowania w pozostałych nowotworach litych. Obecnie wciąż trwające badania III fazy klinicznej mają na celu ocenę skuteczności i bezpieczeństwa terapii TTF w leczeniu niedrobnokomórkowego raka płuc, raka trzustki czy raka jajnika, a także ocenę możliwości wykorzystania TTF w populacji pediatrycznej. Prawdopodobnie możliwości wykorzystania terapii TTF wykraczają poza wymienione jednostki chorobowe, jednakże ustalenie i zbadanie limitów owej terapii wymaga dalszych badań.
Bibliografia
R. L. Siegel, K. D. Miller, N. S. Wagle, and A. Jemal, “Cancer statistics, 2023,” CA Cancer J Clin, vol. 73, no. 1, pp. 17–48, Jan. 2023, doi: 10.3322/caac.21763.
C. Wenger et al., “A Review on Tumor-Treating Fields (TTFields): Clinical Implications Inferred From Computational Modeling,” IEEE Rev Biomed Eng, vol. 11, pp. 195–207, 2018, doi: 10.1109/RBME.2017.2765282.
X. Guo et al., “Tumor-Treating Fields in Glioblastomas: Past, Present, and Future,” Cancers (Basel), vol. 14, no. 15, p. 3669, Jul. 2022, doi: 10.3390/cancers14153669.
J. C. Moser et al., “The Mechanisms of Action of Tumor Treating Fields,” Cancer Res, vol. 82, no. 20, pp. 3650–3658, Oct. 2022, doi: 10.1158/0008-5472.CAN-22-0887.
O. Rominiyi, A. Vanderlinden, S. J. Clenton, C. Bridgewater, Y. Al-Tamimi, and S. J. Collis, “Tumour treating fields therapy for glioblastoma: current advances and future directions,” Br J Cancer, vol. 124, no. 4, pp. 697–709, Feb. 2021, doi: 10.1038/s41416-020-01136-5.
R. Arvind, S. R. Chandana, M. J. Borad, D. Pennington, K. Mody, and H. Babiker, “Tumor-Treating Fields: A fourth modality in cancer treatment, new practice updates,” Crit Rev Oncol Hematol, vol. 168, p. 103535, Dec. 2021, doi: 10.1016/j.critrevonc.2021.103535.
C. Luo, S. Xu, G. Dai, Z. Xiao, L. Chen, and Z. Liu, “Tumor treating fields for high-grade gliomas,” Biomedicine & Pharmacotherapy, vol. 127, p. 110193, Jul. 2020, doi: 10.1016/j.biopha.2020.110193.
J. Trusheim et al., “A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma,” CNS Oncol, vol. 6, no. 1, pp. 29–43, Jan. 2017, doi: 10.2217/cns-2016-0032.
P. Anthony, S. McArdle, and M. McHugh, “Tumor Treating Fields: Adjuvant Treatment for High-grade Gliomas,” Semin Oncol Nurs, vol. 34, no. 5, pp. 454–464, Dec. 2018, doi: 10.1016/j.soncn.2018.10.007.
A. P. Ghiaseddin, D. Shin, K. Melnick, and D. D. Tran, “Tumor Treating Fields in the Management of Patients with Malignant Gliomas,” Curr Treat Options Oncol, vol. 21, no. 9, p. 76, Sep. 2020, doi: 10.1007/s11864-020-00773-5.
M. Giladi et al., “Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells,” Sci Rep, vol. 5, no. 1, p. 18046, Dec. 2015, doi: 10.1038/srep18046.
A. F. Kessler et al., “Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition,” Cell Death Discov, vol. 4, no. 1, p. 77, Jul. 2018, doi: 10.1038/s41420-018-0079-9.
N. Gera, A. Yang, T. S. Holtzman, S. X. Lee, E. T. Wong, and K. D. Swanson, “Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit,” PLoS One, vol. 10, no. 5, p. e0125269, May 2015, doi: 10.1371/journal.pone.0125269.
Y. Zhou et al., “Therapeutic potential of tumor treating fields for malignant brain tumors,” Cancer Rep, vol. 6, no. 5, May 2023, doi: 10.1002/cnr2.1813.
S. Shams and C. B. Patel, “Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields]),” J Mol Cell Biol, vol. 14, no. 8, Dec. 2022, doi: 10.1093/jmcb/mjac047.
N. K. Karanam, L. Ding, A. Aroumougame, and M. D. Story, “Tumor treating fields cause replication stress and interfere with DNA replication fork maintenance: Implications for cancer therapy,” Translational Research, vol. 217, pp. 33–46, Mar. 2020, doi: 10.1016/j.trsl.2019.10.003.
H. Mumblat et al., “Tumor Treating Fields (TTFields) downregulate the Fanconi Anemia-BRCA pathway and increase the efficacy of chemotherapy in malignant pleural mesothelioma preclinical models,” Lung Cancer, vol. 160, pp. 99–110, Oct. 2021, doi: 10.1016/j.lungcan.2021.08.011.
M. Giladi et al., “Tumor treating fields (TTFields) delay DNA damage repair following radiation treatment of glioma cells,” Radiation Oncology, vol. 12, no. 1, p. 206, Dec. 2017, doi: 10.1186/s13014-017-0941-6.
J. S. Kim, J. M. Cho, H. Kim, Y. K. Jeong, J.-K. Kim, and E. H. Kim, “Tumor treating fields can effectively overcome trastuzumab resistant breast cancer multiplication.,” Am J Cancer Res, vol. 11, no. 8, pp. 3935–3945, 2021.
J. Lee, M. M. Grabowski, and J. D. Lathia, “Tumor Treating Fields: killing two birds with one stone,” Journal of Clinical Investigation, vol. 132, no. 8, Apr. 2022, doi: 10.1172/JCI159073.
D. Chen et al., “Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma,” Journal of Clinical Investigation, vol. 132, no. 8, Apr. 2022, doi: 10.1172/JCI149258.
J.-I. Park et al., “Tumor-Treating Fields Induce RAW264.7 Macrophage Activation Via NK-κB/MAPK Signaling Pathways,” Technol Cancer Res Treat, vol. 18, p. 153303381986822, Jan. 2019, doi: 10.1177/1533033819868225.
T. Voloshin et al., “Tumor-treating fields (TTFields) induce immunogenic cell death resulting in enhanced antitumor efficacy when combined with anti-PD-1 therapy,” Cancer Immunology, Immunotherapy, vol. 69, no. 7, pp. 1191–1204, Jul. 2020, doi: 10.1007/s00262-020-02534-7.
T. Kutuk, E. Atak, A. La Rosa, R. Kotecha, M. P. Mehta, and M. D. Chuong, “Tumor treating fields: narrative review of a promising treatment modality for cancer,” Chin Clin Oncol, vol. 12, no. 6, pp. 64–64, Dec. 2023, doi: 10.21037/cco-23-82.
E. H. Kim et al., “Tumor-treating fields induce autophagy by blocking the Akt2/miR29b axis in glioblastoma cells,” Oncogene, vol. 38, no. 39, pp. 6630–6646, Sep. 2019, doi: 10.1038/s41388-019-0882-7.
A. Shteingauz et al., “AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields),” Cell Death Dis, vol. 9, no. 11, p. 1074, Oct. 2018, doi: 10.1038/s41419-018-1085-9.
A. A. Aguilar et al., “Permeabilizing Cell Membranes with Electric Fields,” Cancers (Basel), vol. 13, no. 9, p. 2283, May 2021, doi: 10.3390/cancers13092283.
E. Neuhaus et al., “Alternating Electric Fields (TTFields) Activate Cav1.2 Channels in Human Glioblastoma Cells,” Cancers (Basel), vol. 11, no. 1, p. 110, Jan. 2019, doi: 10.3390/cancers11010110.
E. Chang et al., “Synergistic inhibition of glioma cell proliferation by Withaferin A and tumor treating fields,” J Neurooncol, vol. 134, no. 2, pp. 259–268, Sep. 2017, doi: 10.1007/s11060-017-2534-5.
E. Chang et al., “Tumor treating fields increases membrane permeability in glioblastoma cells,” Cell Death Discov, vol. 4, no. 1, p. 113, Dec. 2018, doi: 10.1038/s41420-018-0130-x.
M. Silginer, M. Weller, R. Stupp, and P. Roth, “Biological activity of tumor-treating fields in preclinical glioma models,” Cell Death Dis, vol. 8, no. 4, pp. e2753–e2753, Apr. 2017, doi: 10.1038/cddis.2017.171.
E. H. Kim, H. S. Song, S. H. Yoo, and M. Yoon, “Tumor treating fields inhibit glioblastoma cell migration, invasion and angiogenesis,” Oncotarget, vol. 7, no. 40, pp. 65125–65136, Oct. 2016, doi: 10.18632/oncotarget.11372.
“Novocure Announces FDA Acceptance of the PMA Application for TTFields Therapy in Non-Small Cell Lung Cancer,” https://www.novocure.com/novocure-announces-fda-acceptance-of-the-pma-application-for-ttfields-therapy-in-non-small-cell-lung-cancer/.
S. Liu et al., “Progress and prospect in tumor treating fields treatment of glioblastoma,” Biomedicine & Pharmacotherapy, vol. 141, p. 111810, Sep. 2021, doi: 10.1016/j.biopha.2021.111810.
L. Benson, “Tumor Treating Fields Technology: Alternating Electric Field Therapy for the Treatment of Solid Tumors,” Semin Oncol Nurs, vol. 34, no. 2, pp. 137–150, May 2018, doi: 10.1016/j.soncn.2018.03.005.
R. Stupp et al., “NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality,” Eur J Cancer, vol. 48, no. 14, pp. 2192–2202, Sep. 2012, doi: 10.1016/j.ejca.2012.04.011.
R. Stupp et al., “Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma,” JAMA, vol. 314, no. 23, p. 2535, Dec. 2015, doi: 10.1001/jama.2015.16669.
S. Kesari and Z. Ram, “Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial,” CNS Oncol, vol. 6, no. 3, pp. 185–193, Jul. 2017, doi: 10.2217/cns-2016-0049.
M. T. Ballo, N. Urman, G. Lavy-Shahaf, J. Grewal, Z. Bomzon, and S. Toms, “Correlation of Tumor Treating Fields Dosimetry to Survival Outcomes in Newly Diagnosed Glioblastoma: A Large-Scale Numerical Simulation-Based Analysis of Data from the Phase 3 EF-14 Randomized Trial,” International Journal of Radiation Oncology*Biology*Physics, vol. 104, no. 5, pp. 1106–1113, Aug. 2019, doi: 10.1016/j.ijrobp.2019.04.008.
R. Miller et al., “Scalp-Sparing Radiation With Concurrent Temozolomide and Tumor Treating Fields (SPARE) for Patients With Newly Diagnosed Glioblastoma,” Front Oncol, vol. 12, Apr. 2022, doi: 10.3389/fonc.2022.896246.
M. Pless, C. Droege, R. von Moos, M. Salzberg, and D. Betticher, “A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer,” Lung Cancer, vol. 81, no. 3, pp. 445–450, Sep. 2013, doi: 10.1016/j.lungcan.2013.06.025.
T. Leal et al., “Tumor Treating Fields therapy with standard systemic therapy versus standard systemic therapy alone in metastatic non-small-cell lung cancer following progression on or after platinum-based therapy (LUNAR): a randomised, open-label, pivotal phase 3 study,” Lancet Oncol, vol. 24, no. 9, pp. 1002–1017, Sep. 2023, doi: 10.1016/S1470-2045(23)00344-3.
G. L. Ceresoli et al., “Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial,” Lancet Oncol, vol. 20, no. 12, pp. 1702–1709, Dec. 2019, doi: 10.1016/S1470-2045(19)30532-7.
F. Rivera, M. Benavides, J. Gallego, C. Guillen-Ponce, J. Lopez-Martin, and M. Küng, “Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: Results of the PANOVA phase 2 study,” Pancreatology, vol. 19, no. 1, pp. 64–72, Jan. 2019, doi: 10.1016/j.pan.2018.10.004.
I. Vergote, R. von Moos, L. Manso, E. Van Nieuwenhuysen, N. Concin, and C. Sessa, “Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: Results of the INNOVATE pilot study,” Gynecol Oncol, vol. 150, no. 3, pp. 471–477, Sep. 2018, doi: 10.1016/j.ygyno.2018.07.018.
M. E. Lacouture et al., “Characterization and Management of Dermatologic Adverse Events With the NovoTTF-100A System, a Novel Anti-mitotic Electric Field Device for the Treatment of Recurrent Glioblastoma,” Semin Oncol, vol. 41, pp. S1–S14, Jun. 2014, doi: 10.1053/j.seminoncol.2014.03.011.
M. E. Lacouture, J. DeNigris, and A. A. Kanner, “Supportive Care in Patients Using Tumor Treating Fields Therapy,” in Alternating Electric Fields Therapy in Oncology, Cham: Springer International Publishing, 2016, pp. 103–116. doi: 10.1007/978-3-319-30576-9_9.
H. M. Babiker, T. Macarulla, P. A. Philip, C. R. Becerra, T. Dragovich, and V. J. Picozzi, “Phase 3 PANOVA-3 study: Tumor treating fields (TTFields) therapy concomitant with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic cancer.,” Journal of Clinical Oncology, vol. 41, no. 16_suppl, pp. TPS4199–TPS4199, Jun. 2023, doi: 10.1200/JCO.2023.41.16_suppl.TPS4199.
I. B. Vergote et al., “Tumour treating fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase III INNOVATE-3/ENGOT-ov50 study,” Annals of Oncology, vol. 30, p. v431, Oct. 2019, doi: 10.1093/annonc/mdz250.067.
W. Shi et al., “Phase 3 TRIDENT study (EF-32): Tumor treating fields (TTFields; 200 kHz) concomitant with chemoradiation, and maintenance TTFields therapy/temozolomide in newly diagnosed glioblastoma.,” Journal of Clinical Oncology, vol. 41, no. 16_suppl, pp. TPS2083–TPS2083, Jun. 2023, doi: 10.1200/JCO.2023.41.16_suppl.TPS2083.
S. Goldman et al., “PDCT-07. FEASIBILITY TRIAL OF TTFIELDS (TUMOR TREATING FIELDS) FOR CHILDREN WITH RECURRENT OR PROGRESSIVE SUPRATENTORIAL HIGH-GRADE GLIOMA (HGG) AND EPENDYMOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM STUDY: PBTC-048,” Neuro Oncol, vol. 20, no. suppl_6, pp. vi201–vi202, Nov. 2018, doi: 10.1093/neuonc/noy148.837.
“ A Phase I Trial of the Optune NovoTTF-200A System With Concomitant Temozolomide and Bevacizumab in Pediatric Patients With High-grade Glioma,” https://clinicaltrials.gov/study/NCT03128047?a=13#more-information.
Zapowiedzi
16 września 2024
Prawa autorskie (c) 2024 Patryk Walocha, Julia Stachowiak, Michał Wilk, Martyna Szlenk
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Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa – Użycie niekomercyjne – Bez utworów zależnych 4.0 Międzynarodowe.
