PIM1 expression is prognostic in clear cell renal cell carcinoma and influenced by an IL-6/JAK/STAT axis

Renal cell carcinoma (RCC) is among the top ten most common cancers diagnosed in the United States. The incidence of RCC has continued to increase in recent years, yet our understanding of its etiology is incomplete. Clear cell RCC (ccRCC) is the major subtype, constituting over 75% of all RCC cases. Treatment options for RCC are limited in efficacy, as RCC tumors typically acquire resistance to current therapies, particularly in advanced and metastatic RCC. von Hippel-Lindeau (VHL) status is the only clinically validated biomarker approved for therapeutic intervention in RCC to date. The identification of novel molecular targets is therefore critical for improving therapeutic strategies for RCC. PIM1 is a constitutively active serine/threonine kinase involved in promoting proliferation, invasion, migration, and apoptosis evasion in cancer. PIM1 expression is dysregulated in ccRCC, contributing to oncogenesis and tumor progression. Here, we explore the influence of PIM1 expression in real-world outcomes of patients with RCC. We identify a link between IL-6 expression and PIM1 expression and activity in human ccRCC tumors and cell lines. Our work provides evidence that targeting an IL-6/JAK/STAT/PIM1 axis may be a viable therapeutic strategy for patients with PIM1-high expressing ccRCC.