Kidney Cancer

The patient and family moved locations before germline testing was done. Effective communication between care teams was essential to ensure continuity, with clear plans established for ongoing surveillance and any additional testing needed for both the child and family.

Interestingly, one antibody exhibited dual-reactive binding to VEGFA and PlGF-2, suggesting a novel therapeutic strategy to prevent PlGF-driven VEGF-resistance. Overall, these antibodies define new mechanisms to disrupt PlGF activity and support a role for NRP1 in cell proliferation.

P=N/A, N=70, Recruiting, Peking University First Hospital

P2, N=18, Active, not recruiting, Emory University | Trial completion date: Jan 2026 --> Dec 2026

FLCN-mutated RCCs comprise a morphologically heterogeneous yet molecularly defined group. Conventional oncoytic morphology was associated with germline alterations while unclassified morphologies could be associated with somatic alterations and possibly germline mutations. FLCN mutations may also be incidental germline mutations in other RCC subtypes. Tumors with unclassified morphologies evoked morphological and immunohistochemical diagnostic consideration of other oncocytic and papillary RCCs and could be associated with adverse outcomes. Recognition may be aided by diffuse GPNMB expression, but definitive classification, especially in cases without conventional morphology, requires molecular testing. These findings broaden the spectrum of FLCN-driven tumors and support their distinction as a unique molecular entity.

Imaging performed after pathologic diagnosis revealed an unsuspected renal mass. This case highlights the importance of recognizing cytomorphologic features suggestive of metastatic renal cell carcinoma during intraoperative consultation and underscores the role of cytologic evaluation in guiding diagnostic workup and tissue management in patients presenting with cervical lymphadenopathy of unknown origin.

Savolitinib plus durvalumab shows OS in MET-driven PRC, supporting the ongoing SAMETA RIII trial (ClinicalTrials.gov identifier: NCT05043090). ctDNA may be a useful predictive biomarker.

These findings advance our understanding of genetic susceptibility to different cancers. Future work in larger, more diverse GWAS, coupled with more comprehensive annotation atlases, is essential to expand upon and validate our results.

Clear cell renal cell carcinoma (ccRCC) with von Hippel-Lindau (VHL) loss exhibits TBK1 dependency, and targeted therapeutic strategies outside of HIF-2α inhibition have remained limited. In this issue of Cell Chemical Biology, Liao et al.1 describe a second-generation cereblon-recruiting TBK1 proteolytic targeting chimera (PROTAC) with promising pre-clinical activity.

This study suggests that LOT may originate from principal cells of the collecting duct and distal renal tubule. Morphologically, it is characterized by a nested growth pattern with stromal edema, and immunohistochemically, it shows positivity for CK7 and negativity for CD117. The consistent positive expression of L1CAM in this study serves as a useful complementary marker for the differential diagnosis of LOT from other morphologically similar eosinophilic renal tumors. Regarding molecular genetics, this study not only explored the characteristics of mTOR pathway gene mutations in LOT but also identified one case with non-mTOR pathway-related molecular alterations, providing new supplementary information for the molecular landscape of LOT. Considering the cellular origin and indolent biological behavior of LOT, these findings contribute to further refinement of the classification system and nomenclature for this type of tumor. Additionally, this study provides important case data supporting LOT in the Chinese population.

Two cycles of nivolumab plus ipilimumab were performed before discovering severe cervical spine pain. Here we show (1) robust CD3+ and CD20+ infiltration in primary tumors and metastases, with immune cells in direct contact with tumor cells or organized in lymphoid aggregates/tertiary lymphoid structures; (2) PD-L1 overexpression in sRCC and nodal metastasis but absent in post-immunotherapy bone lesions; (3) increased CD163+ macrophages in sRCC and metastases versus ccRCC. This case illustrates that ICIs can induce near-complete eradication of bone metastases; that bone is not an immune-exempt organ, with massive intratumoral immune cell infiltration; and that immediate immune-mediated tumor clearance prevents structural skeletal damage, which merits careful surveillance.

After receiving targeted combination immunotherapy with sequential PD-1 inhibitors (toripalimab) plus anti-angiogenic agents (sunitinib, axitinib)-a regimen that enhances anti-tumor immunity but may disrupt pulmonary immune homeostasis-the patient gradually developed progressive dyspnea, chest tightness, hypoxemia, and anuria. Although PJP complicated by hydropneumothorax after immunotherapy is rare, it should be considered as a possible etiology when cancer patients develop progressive dyspnea with difficulty maintaining oxygen saturation after receiving immune checkpoint inhibitor-based therapy, particularly in the context of immune checkpoint inhibitor use. While biomarkers for predicting immunotherapy efficacy and irAEs are well-studied, the identification of specific biomarkers for predicting opportunistic infections like PJP in this context remains an area of active research.