Prostate cancer has distinct genetic properties in different groups of men that could be targeted to improve patient outcomes, new research suggests.

Researchers in Nikolaus Rajewsky’s lab at Max Delbrück Center combined high-resolution, single-cell spatial technologies to map a tumor’s cellular neighborhoods in 3D and identify potential targets for personalized cancer therapy. They describe their findings in two separate papers in Cell Systems.

The tumor microenvironment (TME) consists of a complex mix of cellular and non-cellular components, including immune cells, stromal cells, extracellular matrix, cytokines, and growth factors. These elements interact with tumor cells to influence tumorigenesis, growth, invasion, and metastasis. Long noncoding RNAs (lncRNAs)—a class of non-coding RNAs longer than 200 nucleotides—have attracted considerable attention for their roles in regulating gene expression at the epigenetic, transcriptional, and post-transcriptional levels. Emerging evidence suggests that lncRNAs are crucial in shaping the TME by modulating processes such as immune evasion, angiogenesis, metabolic reprogramming, and the maintenance of cancer stem cells. This review provides an overview of the current understanding of lncRNAs in the TME, focusing on their involvement in key signaling pathways and cellular interactions that drive tumor progression. We discussed how lncRNAs contribute to extracellular matrix remodeling, facilitate communication between tumor and stromal cells, and regulate immune cell infiltration and function within the TME. Additionally, we explore the potential of lncRNAs as biomarkers for early cancer detection and prognosis, as well as their promise as therapeutic targets to disrupt tumor-microenvironment crosstalk. The review also addresses challenges in targeting lncRNAs therapeutically, such as ensuring specificity, minimizing off-target effects, and achieving effective in vivo delivery of lncRNA-targeted therapies. Strategies to overcome these challenges include the development of highly specific lncRNA knockout technologies and the use of advanced delivery systems, such as nanoparticles and viral vectors, to precisely target tumor-associated cells. Overall, this review underscores the significant role of lncRNAs in the TME and their potential as novel tools for enhancing cancer diagnosis and treatment. By elucidating the multifaceted roles of lncRNAs in the TME, we aimed to provide insights that could lead to more effective, targeted therapeutic strategies, ultimately advancing cancer research and improving patient care.

Moffitt Cancer Center has launched The ImmunoVerse, a new podcast hosted by President and CEO Patrick Hwu, M.D. A world-renowned physician-scientist and tumor immunologist, Hwu will bring immunotherapy discoveries to life through the voices of those advancing the groundbreaking field.