Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments
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Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments. / Talwelkar, Sarang S.; Mäyränpää, Mikko I.; Søraas, Lars; Potdar, Swapnil; Bao, Jie; Hemmes, Annabrita; Linnavirta, Nora; Lømo, Jon; Räsänen, Jari; Knuuttila, Aija; Wennerberg, Krister; Verschuren, Emmy W.
In: Cell Reports Medicine, Vol. 2, No. 8, 100373, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments
AU - Talwelkar, Sarang S.
AU - Mäyränpää, Mikko I.
AU - Søraas, Lars
AU - Potdar, Swapnil
AU - Bao, Jie
AU - Hemmes, Annabrita
AU - Linnavirta, Nora
AU - Lømo, Jon
AU - Räsänen, Jari
AU - Knuuttila, Aija
AU - Wennerberg, Krister
AU - Verschuren, Emmy W.
N1 - Publisher Copyright: © 2021 The Author(s)
PY - 2021
Y1 - 2021
N2 - Functional profiling of a cancer patient's tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM+ epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.
AB - Functional profiling of a cancer patient's tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM+ epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.
KW - ALK
KW - drug sensitivity and resistance testing
KW - EGFR
KW - ex vivo drug screening
KW - functional diagnostics
KW - KRAS
KW - lung cancer
KW - personalized medicine
KW - pharmacogenomics
KW - targeted therapy
U2 - 10.1016/j.xcrm.2021.100373
DO - 10.1016/j.xcrm.2021.100373
M3 - Journal article
C2 - 34467250
AN - SCOPUS:85112829958
VL - 2
JO - Cell Reports Medicine
JF - Cell Reports Medicine
SN - 2666-3791
IS - 8
M1 - 100373
ER -
ID: 279634752