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Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal cell carcinoma, accounting for nearly 70–90% of cases and the majority of metastatic RCC worldwide. Despite advances in surgery and immunotherapy, metastatic ccRCC remains challenging to treat and accounts for the majority of RCC-related deaths. A hallmark of ccRCC biology is dysregulated hypoxia signaling, largely driven by loss of the tumor suppressor VHL, which leads to accumulation of hypoxia-inducible factors (HIFs) and activation of downstream oncogenic pathways.
Recent studies have turned attention to doublecortin-like kinase 1 (DCLK1), a serine/threonine kinase and recognized marker of cancer stem cells. DCLK1 is known to confer stem-like characteristics on tumor cells, thereby enhancing their capacity for proliferation, invasion, and metastasis. However, the mechanisms regulating its expression and the therapeutic implications of targeting DCLK1 have remained poorly defined.
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