Journal Article Epublish 1 citation
PubMed: 40710201 DOI: 10.3390/curroncol32070391
Treatment-Induced Gene Expression Changes in Metastatic Renal Cell Carcinoma: Insights from a Syngeneic Mouse Model.
Curr Oncol 32(7)
Authors: Ko Okabe, Toshiaki Tanaka, Tetsuya Shindo, Yuki Kyoda, Sachiyo Nishida, Kohei Hashimoto, Ko Kobayashi, Naoya Masumori
Affiliations
- Department of Urology, Sapporo Medical University, South-1, West-16, Chuo-ku, Sapporo 060-8543, Japan.
Abstract
This study aimed to clarify the alterations in gene expression in metastatic renal cell carcinoma (mRCC) during disease progression and in response to treatment with immune checkpoint inhibitors using a syngeneic mouse mRCC model. RENCA cells were orthotopically implanted in BALB/c mice. Mice received first-line treatment with cabozantinib, anti-PD-1 antibody, or a combination. Tumor progression was monitored using serial micro-computed tomography. Lung metastasis samples were collected, and RNA sequencing was performed. Mice with apparent disease progression received second-line treatment with axitinib, everolimus, or lenvatinib after combination therapy. The median overall survival was 28, 34, 34, and 49 days in untreated mice and those treated with cabozantinib, anti-PD-1, or their combination, respectively (p < 0.05). RNA sequencing revealed upregulation of the fibroblast growth factor pathway in lung metastases after monotherapy, whereas mTOR pathway activation was observed only after combination therapy. Treatment-specific gene expression changes occur in mRCC, suggesting that the optimal target for sequential therapy in mRCC varies depending on prior treatment.
MeSH
Cells, Genes, Neoplasms, Disease Progression, Carcinoma, Renal Cell, Immune Checkpoint Inhibitors, Neoplasm Metastasis, Therapeutics, Gene Expression