15 juni 2025: Bron: Mesothelioma website
Tumor Treating Fields, ook bekend als TTFields, is een vorm van een kankerbehandeling die is goedgekeurd door de Amerikaanse Food and Drug Administration (FDA) voor de behandeling van in de longen genestelde mesothelioma - asbestkanker. Tumor Treating Fields blijkt effectief in combinatie met chemotherapie om de groei van de kwaadaardige kankercellen te beperken en de overleving te verbeteren. Zo schrijft de website Mesothelioma.com op hun voorpagina.
De nieuwste studie is gepubliceerd januari 2025.
Zo schrijven de auteurs in het abstract o.a.: "In deze studie hebben we aangetoond dat gelijktijdige blootstelling aan TTFields en doxorubicine of vinorelbine de werkzaamheid van de behandeling in van patiënten afkomstige PM-cellen - pleurale mesothelioma verbeterde door de intracellulaire geneesmiddelconcentraties te verhogen. Met behulp van specifieke, gevoelige en kwantitatieve analyse echnieken observeerden we een toename van meer dan 70% in de intracellulaire concentraties van doxorubicine of vinorelbine in met TTFields behandelde monsters, en een toename van meer dan 50% in de geneesmiddelopname in cellen die werden blootgesteld aan TTFields en pemetrexed."
Ze schrijven ook dat een gelijktijdige blootstelling aan het geneesmiddel en TTFields belangrijk blijkt voor het verhogen van de intracellulaire geneesmiddelconcentraties om de antiproliferatieve effecten van de behandeling te versterken.
Het volledige studieverslag is in PDF formaat gratis in te zien of te downloaden. Klik daarvoor op de titel:
Am J Cancer Res 2025;15(1):271-285 www.ajcr.us /ISSN:2156-6976/ajcr0158988 https://doi.org/10.62347/ODWL5634
Original Article:
Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells
Rosy Amodeo1,2, Lavinia Morosi1 , Marina Meroni3 , Ezia Bello3 , Sara Timo4 , Roberta Frapolli3 , Maurizio D’Incalci1,2*, Monica Lupi1* 1Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy; 2Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy; 3Laboratory of Cancer Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy; 4Metabolomics and Pharmacokinetics Unit, IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy. *Equal contributors. Received July 5, 2024; Accepted September 4, 2024; Epub January 15, 2025; Published January 30, 2025
Abstract:
Tumor Treating Fields (TTFields) applied with standard chemotherapy have been approved for the firstline treatment of unresectable pleural mesothelioma (PM), an aggressive malignancy with limited effective therapy options. In this study, we demonstrated that the simultaneous exposure to TTFields and doxorubicin or vinorelbine enhanced treatment efficacy in patient-derived PM cells by increasing intracellular drug concentrations. This was achieved by modulating several genes that encode transport proteins, such as the downregulation of P-glycoprotein (P-gp). Using specific, sensitive and quantitative analytical techniques, we observed a more than 70% increase in intracellular concentrations of doxorubicin and vinorelbine in samples treated with TTFields, and a greater than 50% increase in drug uptake in cells exposed to TTFields and pemetrexed. This result indicates that the increased drug concentration observed in TTFields treated cells is significant not only for drugs that are P-gp substrates but also suggests that TTFields could potentially affect other efflux pumps. However, the co-exposure to the drug and TTFields was critical to increasing intracellular drug levels, highlighting the necessity of concurrent use with drugs to enhance the antiproliferative effects of treatment. The in vitro findings were further corroborated by in vivo pharmacokinetic experiments in mice subcutaneously injected with epithelioid PM tumors. Indeed, a 30% increase in intratumor concentrations was observed when vinorelbine was administered with TTFields.
Conclusion:
Our findings suggest that TTFields could be a well-tolerated approach for enhancing intratumoral drug levels and potentially achieving a more significant therapeutic impact on PM treatment.
Disclosure of conflict of interest None. Address correspondence to: Monica Lupi, Laboratory of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milano, Italy. E-mail: monica.lupi@humanitasresearch.it
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