AUA 2022: Development of Patient-Derived Kidney Cancer Organoid; Application to Drug Screening Models and Its Challenges

(UroToday.com)  The 2022 American Urological Association Annual Meeting included a kidney cancer session featuring work from Dr. Akira Kazama and colleagues presenting results of their study investigating the development of 3D tumor organoids from renal cell carcinoma (RCC) tumors. While surgical resection of localized RCC can be curative, up to one-third of patients eventually recur. This raises the question of how treatment for a particular patient can become personalized and improve over time. Thus, these tumor organoids are being developed with the hopes that they will behave similarly to the primary RCC tumors and serve as reliable models. This exciting work has the potential to serve many purposes as they tested tyrosine kinase inhibitors (TKIs), targeted therapeutics for metastatic RCC, and for drug testing. Attempting to improve the life prognosis of patients diagnosed with RCC, this study seeks to address the challenges in developing personalized therapy for these patients.

 

Surgical tumor specimens were obtained from 20 patients with RCC. In the present study, samples were collected by partial nephrectomy because organoids cannot grow without sufficient tumor volume. Dr. Kazama noted that in clinical practice, many patients undergo only core biopsy in advanced cases. Thus, it becomes necessary to further develop the protocol to establish and culture tumor organoids even from a small sample volume. This would also serve to increase the applicability of this technique. After ex vivo development from freshly resected RCC tumors, their histopathological and molecular characteristics were evaluated using histological staining and whole exome sequencing. The therapeutic efficacy of TKIs in RCC tumor organoids was determined by a cell viability assay.

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It is interesting to note that RCC tumor organoids recapitulated the histological architecture of the primary tumor, providing evidence for the use of this model. Because of the exome sequencing, they identified a strong concordance of primary tumors and the corresponding tumor organoids at the genetic level as well.

 

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The RCC tumor organoids responded differently to targeted therapeutics, thus showing patient-specific sensitivity to the treatment. In addressing the replicability of drug treatment, Dr. Kazama noted that the present model does not replicate the tumor microenvironment (such as the tumor vasculature and immune cells), rendering it difficult to evaluate the effect of TKIs inhibition on angiogenesis.

To conclude the presentation, Dr. Kazama states that the present study was able to demonstrate the development of a patient-derived tumor organoid culture of RCC. Additionally, this novel approach for the ex vivo evaluation has the potential for the selection of personalized therapy. With a few very thoughtful remarks, Dr. Yoshihiko Tomita, principal investigator for the project, stepped up to the microphone to comment on future directions for this novel approach. He admitted that one of the biggest drawbacks to this work is that the process of growing tumor organoids is time intensive. If a patient is discovered to have metastasizing cancer, the low efficiency of this technique removes itself as an effective tool in those circumstances. The response is then to create organoids for high-risk patients. In the case that the individual does develop metastatic cancer, the previously prepared organoids would be well utilized as drug testing models before use of these treatments. Dr. Tomita believes that this strategy would provide patients with the most benefit from this novel approach.

 

Presented by: Akira Kazama, MD, Department of Urology, Division of Molecular Oncology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Co-Authors: Vladimir Bilim, Yoshihiko Tomita

Written by: Kelvin Vo, Department of Urology, University of California Irvine, @kelvinvouci on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

References:
1. Akira Kazama, Vladimir Bilim, Yoshihiko Tomita. Development of patient-derived kidney cancer organoid; Application to drug screening models and its challenges [abstract]. In: American Urological Association Annual Meeting, May 13-16, 2022, New Orleans, Louisiana

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