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s41467-020-16952-9.pdf (1.78 MB)

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2020-06-22

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cc-by (c) Fernandes Neto et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/166904

Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours

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https://doi.org/10.1038/s41467-020-16952-9

Resum

Resistance to targeted cancer drugs is thought to result from selective pressure exerted by a high drug dose. Partial inhibition of multiple components in the same oncogenic signalling pathway may add up to complete pathway inhibition, while decreasing the selective pressure on each component to acquire a resistance mutation. We report here testing of this Multiple Low Dose (MLD) therapy model in EGFR mutant NSCLC. We show that as little as 20% of the individual effective drug doses is sufficient to completely block MAPK signalling and proliferation when used in 3D (RAF + MEK + ERK) or 4D (EGFR + RAF + MEK + ERK) inhibidor combinations. Importantly, EGFR mutant NSCLC cells treated with MLD therapy do not develop resistance. Using several animal models, we find durable responses to MLD therapy without associated toxicity. Our data support the notion that MLD therapy could deliver clinical benefit, even for those having acquired resistance to third generation EGFR inhibidor therapy.

Matèries

Resistència als medicaments, Tumors

Matèries (anglès)

Drug resistance, Tumors

Citació

Neto, J. M. F., Nadal, E., Bosdriesz, E., Ooft, S. N., Farre, L., McLean, C., ... & Felip, E. (2020). Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours. Nature Communications, 11(1), 1-9.

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

FERNANDES NETO, João m., NADAL, Ernest, BOSDRIESZ, Evert, OOFT, Salo n., FARRÉ, Lourdes, MCLEAN, Chelsea, KLARENBEEK, Sjoerd, JURGENS, Anouk, HAGEN, Hannes, WANG, Liqin, FELIP, Enriqueta, MARTÍNEZ MARTÍ, Alex, VIDAL-BEL, August, VOEST, Emile, WESSELS, Lodewyk f. a., VAN TELLINGEN, Olaf, VILLANUEVA GARATACHEA, Alberto, BERNARDS, René. Multiple low dose therapy as an effective strategy to treat EGFR inhibitor-resistant NSCLC tumours. _Nature Communications_. 2020. Vol. 11, núm. 1, pàgs. 1-9. [consulta: 20 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/166904]

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