Precision oncology using organoids of a secretory carcinoma of the salivary gland treated with TRK-inhibitors. (February 2023)

• Record Type: Journal Article
• Authors: Lassche, Gerben; van Engen - van Grunsven, Adriana C.H.; van Hooij, Onno; Aalders, Tilly W.; AM Weijers, Jetty; Cocco, Emiliano; Drilon, Alexander; Hoischen, Alexander; Neveling, Kornelia; Schalken, Jack A.; Verhaegh, Gerald W.; van Herpen, Carla M.L.
• Is Part Of: Oral oncology. Volume 137(2023)
• Publication Date: 2023-02
• Subjects: Organoids [Mesh] -- Salivary gland neoplasms [Mesh] -- Precision medicine [Mesh] -- NTRK3 receptor [Mesh]; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2022.106297
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: We describe the first NTRK3 fusion positive organoid model for secretory carcinoma; The model was used to in vitro predict the in vivo drug response to larotrectinib; The importance of thorough characterization of organoids was illustrated; Characterization is required prior to extrapolating in vitro findings to the clinic. Abstract: The use of anticancer drugs targeting specific molecular tumor characteristics is rapidly increasing in clinical practice, but selecting patients to benefit from these remains a challenge. It has been suggested that organoid cultures would be ideally suited to test drug responses in vitro . Here we describe and characterize in depth a case of ETV6-NTRK3 gene fusion-positive secretory carcinoma of the salivary glands and corresponding organoid cultures that responded and subsequently acquired resistance to TRK targeting therapy with larotrectinib. This case-culture-characterization illustrates the advances made in precision oncology, but also exposes important caveats in using organoids to predict treatment response.