Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Patient-Derived Free-Floating Non-Small Cell Lung Cancer Organoids: A Versatile Tool for Personalized Testing of Chemotherapeutic Drugs

Lilian Ismail
ORCID logo ,
Komal Zahid
,
Anna Polyanskaya
ORCID logo ,
Aya Al Othman
,
Ningfei Shen
,
Xiaoli Qi
,
Rushan A. Sulimanov
,
Yuri Esakov
,
Vladimir A. Makarov
,
Gleb I. Filkov
,
Alexander V. Trofimenko
,
Alexandre Mezentsev
,
Mikhail Durymanov
* ORCID logo
Version 1 : Received: 28 December 2023 / Approved: 29 December 2023 / Online: 29 December 2023 (13:28:30 CET)

How to cite: Ismail, L.; Zahid, K.; Polyanskaya, A.; Al Othman, A.; Shen, N.; Qi, X.; Sulimanov, R.A.; Esakov, Y.; Makarov, V.A.; Filkov, G.I.; Trofimenko, A.V.; Mezentsev, A.; Durymanov, M. Patient-Derived Free-Floating Non-Small Cell Lung Cancer Organoids: A Versatile Tool for Personalized Testing of Chemotherapeutic Drugs. Preprints 2023, 2023122280. https://doi.org/10.20944/preprints202312.2280.v1 Ismail, L.; Zahid, K.; Polyanskaya, A.; Al Othman, A.; Shen, N.; Qi, X.; Sulimanov, R.A.; Esakov, Y.; Makarov, V.A.; Filkov, G.I.; Trofimenko, A.V.; Mezentsev, A.; Durymanov, M. Patient-Derived Free-Floating Non-Small Cell Lung Cancer Organoids: A Versatile Tool for Personalized Testing of Chemotherapeutic Drugs. Preprints 2023, 2023122280. https://doi.org/10.20944/preprints202312.2280.v1

Abstract

Patient-derived tumor organoids (PDTOs) are a novel preclinical model of non-small cell lung cancer (NSCLC) for studying tumor biology and precision medicine, which recapitulates tumor morphology and gene expression profile. However, some issues such as low establishment rates, long-term production, and the loss of the immune microenvironment have hindered their widespread practical use. In this study, we investigated the efficacy of a recently introduced free-floating organoid production method to address these issues. The free-floating approach provided PDTO establishment success rate of over 90 % resulting in organoid formation within a short period of one week. These organoids retained the elements of the parental tumor morphology and contained stroma and immune cell populations, as confirmed by flow cytometry analysis. Importantly, we found that the cytokine and growth factor expression profiles of the free-floating organoids correlated with those of the original tumors in 58 % of cases, indicating the preservation of tumor-associated signaling pathways. Obtained organoids exhibited different responses to anticancer chemotherapeutics that might be a result of variable expression of drug resistance-associated genes. Considering the high establishment rate and short time of free-floating organoid production, this technique provides a valuable tool for a more accurate evaluation of therapeutic strategies and cancer biology studies.

Keywords

Free-floating organoids; non-small cell lung cancer; cytokine; drug resistance; personalized medicine

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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