The RNA-Binding Protein ELAVL4/HuD Promotes Stress-Associated Tumor Survival in Neuroendocrine Cancers

Neuro-endocrine-related cancers overexpress ELAVL4 (HuD), a neuron-specific RBP implicated in post-transcriptional regulation. HuD plays a role in tumor cell survival; its knockdown in cancer cells and tumors leads to reduced growth and viability. In this review, we addressed HuD's role in several molecular pathways that contribute to the development of cancer. For example, cancer cells that have high levels of HuD are able to better withstand stressful tumor microenvironments because HuD stabilizes certain mRNAs, which promotes tumor development, modulates oxidative and metabolic stress, enhances autophagy, and impairs apoptosis. We discussed future studies on HuD in cancer, which should focus on its diverse roles in various cancer types and the molecular aspects. Furthermore, assessing HuD's contribution to the efficacy of immunotherapy requires an understanding of how it affects immune responses in malignancies. The development of targeted therapies, such as RNA-based approaches and small molecules, offers intriguing avenues for precision cancer management. The transition of HuD-directed therapies from preclinical models to clinical trials is anticipated to be accelerated by ongoing advancements in RNA-targeted drug discovery, structural biology, medicinal chemistry, and targeted drug delivery, even though no HuD-specific therapies have yet entered standard clinical practice.