bims-raghud 2025-10-26 papers

Issue of 2025–10–26
three papers selected by
Irene Sambri, TIGEM

World J Surg Oncol. 2025 Oct 21. 23(1): 385

MED15-TFE3 rearranged renal cell carcinoma: a subtype of TFE3-rearranged renal cell carcinoma with unique clinicopathologic features and better prognosis.

Zhenggen Deng, Yanhao Xu, Enjia Duan, Xiaopo Zhang, Xiang Dong, Hongqian Guo, Weidong Gan.

BACKGROUND: MED15-TFE3 rearranged renal cell carcinoma (MED15-TFE3 rRCC) is a rare subtype of TFE3-rearranged renal cell carcinoma (TFE3 rRCC). To date, only 47 cases of MED15-TFE3 rRCC (including 2 cases from our institution) have been reported worldwide.
METHODS: Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RNA sequencing, we aimed to identify whether TFE3 rRCC patients at our institution harbor the MED15-TFE3 gene fusion. We will perform a statistical analysis of the pathological features, imaging findings, and clinical outcomes of all published cases of MED 15-TFE rRCC.
RESULTS: MED15-TFE3 rRCC typically has a cystic and solid (predominantly cystic) architecture. The tumor cells feature round nuclei with inconspicuous nucleoli, abundant cytoplasm, and clear to eosinophilic staining. Immunohistochemically, 38 of 39 patients had positive nuclear staining for TFE3, and 37 of 38 patients were positive for PAX8. The FISH assay was positive for rearrangement (red-green signal separation). RNA sequencing identified the MED15-TFE3 fusion gene. One pediatric patient presented with preoperative hilar lymph node metastasis. During follow-up, only one patient developed metastatic disease.
CONCLUSIONS: In contrast to traditional TFE3 rRCCs, MED15-TFE3 rRCCs may have distinctive clinicopathological features and a better prognosis. These findings enhance our understanding of the heterogeneity of TFE3 rRCCs.

Keywords: MED15-TFE3 ; TFE3 ; rRCC (rearranged renal cell carcinoma); clinicopathologic; prognosis

DOI: https://doi.org/10.1186/s12957-025-04048-x

Am J Physiol Cell Physiol. 2025 Oct 20.

The role of the fibroblast in cardiorenal syndrome.

Karin Åvall, Julie M Williams.

The diversity of fibroblasts across different organs, and within the same structures, means that their role in both health and disease is manifold. This review focusses on their job in the heart and kidney, specifically during the course of cardiorenal syndrome (CRS). During CRS there is a complex bidirectional interplay between the two body systems whereby the failure of one drives the decline of the other. These effects are manifest by a response that leads to the deposition of fibrotic tissue, attributable to fibroblast dysfunction. Fibroblasts in themselves provide essential functions within organs, which are determined by the specific identity of their subtype. During disease fibroblast function is further constrained and directed by the niches that form at the sites of injury. This review delves into the origins of fibroblasts in heart and kidney, their functions in each tissue and the processes and stressors whereby they become activated to form myofibroblasts. We discuss tools that can be used to study the phenomenon of fibroblast activation in vitro and in human studies and, finally, what therapeutic possibilities there may be in the future.

Keywords: Cardiorenal syndrome; fibroblasts; fibrosis; heart; kidney

DOI: https://doi.org/10.1152/ajpcell.00441.2025

Cancer Discov. 2025 Oct 21.

p53 drives lung cancer regression through a TSC2/TFEB-dependent senescence program.

Mengxiong Wang, Kathryn T Bieging-Rolett, Alyssa M Kaiser, Colleen A Brady, John H Lockhart, Sofia Ferreira, Kha T Nguyen, Arati Rajeevan, Simone A Evans, Tianyu Zhao, Nitin Raj, Arielle Elkrief, Sam E Tischfield, Marc Ladanyi, Michael G Ozawa, Nam Q Bui, Christopher T Chen, Elsa R Flores, Laura D Attardi.

Pharmacological restoration of p53 tumor suppressor function is a conceptually appealing therapeutic strategy for the many deadly cancers with compromised p53 activity, including lung adenocarcinoma (LUAD). However, the p53 pathway has remained undruggable, partly because of insufficient understanding of how to drive effective therapeutic responses without toxicity. Here, we use mouse and human models to deconstruct the transcriptional programs and sequelae underlying robust therapeutic responses in LUAD. We show that p53 drives potent tumor regression by direct Tsc2 transactivation, leading to mTORC1 inhibition and TFEB nuclear accumulation, which in turn triggers lysosomal gene expression programs, autophagy, and cellular senescence. Senescent LUAD cells secrete factors to recruit macrophages, precipitating cancer cell phagocytosis and tumor regression. Collectively, our analyses reveal a surprisingly complex cascade of events underlying a p53 therapeutic response in LUAD and illuminate targetable nodes for p53 combination therapies, thus establishing a critical framework for optimizing p53-based therapeutics.

DOI: https://doi.org/10.1158/2159-8290.CD-25-0525