The urothelial gene regulatory network: understanding biology to improve bladder cancer management

Ramal, Maria; Corral, Sonia; Kalisz, Mark; Lapi, Eleonora; Real, Francisco X.

doi:10.1038/s41388-023-02876-3

Cited by 2 publications

(1 citation statement)

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“…TP63, belonging to the p53 gene family together with p73, encodes different proteins capable of either activating p53-responsive genes or acting as a dominant-negative factor against p53 [ 39 ]. p63 shows a vital function in the typical development and upkeep of the human urothelium [ 40 ]. However, regarding bladder carcinoma, the impact of mutations in the p63 gene remains controversial for the scanty information available.…”

Section: Case Presentation and Discussionmentioning

confidence: 99%

Molecular profiling of a bladder cancer with very high tumour mutational burden

Scimeca,

Bischof,

Bonfiglio

et al. 2024

Cell Death Discov.

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The increasing incidence of urothelial bladder cancer is a notable global concern, as evidenced by the epidemiological data in terms of frequency, distribution, as well as mortality rates. Although numerous molecular alterations have been linked to the occurrence and progression of bladder cancer, currently there is a limited knowledge on the molecular signature able of accurately predicting clinical outcomes. In this report, we present a case of a pT3b high-grade infiltrating urothelial carcinoma with areas of squamous differentiation characterized by very high tumor mutational burden (TMB), with up-regulations of immune checkpoints. The high TMB, along with elevated expressions of PD-L1, PD-L2, and PD1, underscores the rationale for developing a personalized immunotherapy focused on the use of immune-checkpoint inhibitors. Additionally, molecular analysis revealed somatic mutations in several other cancer-related genes, including TP53, TP63 and NOTCH3. Mutations of TP53 and TP63 genes provide mechanistic insights on the molecular mechanisms underlying disease development and progression. Notably, the above-mentioned mutations and the elevated hypoxia score make the targeting of p53 and/or hypoxia related pathways a plausible personalized medicine option for this bladder cancer, particularly in combination with immunotherapy. Our data suggest a requirement for molecular profiling in bladder cancer to possibly select appropriate immune-checkpoint therapy.

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Section: Case Presentation and Discussionmentioning

confidence: 99%