Cancer of the prostate is an important issue on a global scale, and therefore the identification of targets to support the development of therapy for this cancer should be a priority, particularly given the rise in cases of advanced prostate cancer and of patients who have developed resistance to the current standard of care therapies. Protein kinases have been the most heavily researched and targeted class of drug candidates in oncology, and they play a pivotal role in cellular signaling. This review examines Protein Serine Kinase H1 (PSKH1), which is an example of a member of the 'dark kinome' that is not extensively studied. PSKH1 recently emerged as a major component of cancer development. Functional RNAi screens demonstrated that PSKH1 enhances proliferation in both androgen-dependent and castration-resistant prostate cancer models. PSKH1's mechanism of action is distinct, as it has two major regulatory nodes: Calcium-dependent phosphorylation by Calmodulin activates it, and Reticulocalbin-3 inhibits PSKH1 through protein-protein interactions. Additionally, PSKH1 activates several pro-survivals signaling pathways (such as p38 MAPK) and regulates alternative splicing of pre-mRNAs in cancer. This review will summarize recent studies relating to the importance of PSKH1 as a potential therapeutic target for prostate cancer. This study discusses PSKH1's general biochemistry, its association with cancer, and the signaling pathways it regulates. Moreover, this study presents a multi-pronged approach linking how it can be inhibited therapeutically, including ATP-competitive and allosteric inhibition, protein- protein interaction displacement, protein degraders (PROTACs), and nucleic acid therapeutics. This study proposes that PSKH1 inhibition represents a novel treatment opportunity to simultaneously interfere with multiple oncogenic pathways and is expected to circumvent resistance and potentiate other treatments. Lastly, this study presents a roadmap of future studies to clinically validate PSKH1 and fast-track the discovery of first-in-class inhibitors of this novel target.

Prime editing (PE), as a transformative genome-editing technology, overcomes many of the limitations of CRISPR-Cas9, particularly by enabling high-fidelity base conversions independent of double-strand breaks (DSBs). This unique mechanism significantly reduces unintended insertions, deletions, and chromosomal rearrangements, positioning PE as a safer and more precise tool for therapeutic gene correction. Recently, the world's first FDA-approved PE clinical trial (PM359 for chronic granulomatous disease) was officially launched, representing a major milestone in the field and highlighting the growing clinical translational potential of PE for treating human genetic disorders. Since the introduction of PE technology, extensive research efforts have been devoted to improving its gene correction efficiency, expanding the editing window, broadening target-site compatibility, reducing the size of the editing protein, and optimizing in vivo delivery vector systems. This review systematically summarizes the key improvements and evolutionary progress in the prime editor design and its updated delivery systems, with a particular focus on innovative modifications that have successfully overcome technical barriers. This study also highlights recent advances in engineered PE variants and their derivative systems, which have collectively expanded the scope and precision of PE-mediated gene correction. Additionally, this study critically discusses the remaining limitations and challenges associated with its application.

Adenine base editors (ABEs), which achieve A·T to G·C conversions in the genome precisely, symbolize a groundbreaking development in genetic engineering across animal, plant, and microbial systems. This review systematically summed up the research progress and current challenges of ABE in medical and biological applications: it outlined the historical context and pivotal milestones of its technological development; it emphasized major therapeutic advances for genetic diseases including spinal muscular atrophy, mitochondrial genetic disorders, and hyperlipidemia; it provided a comprehensive overview of its prospective uses for enhancing genetic traits in agricultural crops, including grains and fruits; this review conducted a multidimensional assessment of ABE performance through systematic comparison with other base editing technologies, comprehensively evaluating both editing efficiency and inherent limitations. It specifically addresses biosecurity risks such as off-target effects and genomic instability. Finally, safety concerns were proposed as the central challenge hindering its clinical translation, although ABE holds immense promise for precision medicine and agricultural breeding. Unlike previous reviews that mainly summarized early ABE development and general applications, this review particularly emphasizes recently engineered ABE systems, translational bottlenecks, delivery strategies, comparative clinical feasibility, and unresolved biosafety challenges that currently limit broader therapeutic and agricultural applications.

Small interfering RNA (siRNA) and messenger RNA (mRNA) therapeutics represent transformative approaches in precision pharmacology, enabling targeted gene silencing and protein expression, respectively. This review provides a comprehensive analysis of their molecular mechanisms, delivery strategies, clinical applications, and future directions. By leveraging RNA interference for siRNA and translational machinery for mRNA, these therapeutics address previously untreatable diseases, including genetic disorders, cancers, and infectious diseases. Advances in nanoparticle- based delivery systems, such as lipid nanoparticles, have overcome historical barriers like RNA instability and immune activation. Current clinical applications, including FDA-approved therapies, highlight their efficacy, while ongoing challenges, such as off-target effects and scalable production, are discussed. Future directions emphasize personalized medicine, combination therapies, and novel delivery platforms to enhance therapeutic precision and accessibility.

Osteosarcoma (OS) is the most common form of primary bone malignancy, characterized by the production of osteoid tissue and contributing significantly to cancer-related mortality in both pediatric and adult populations. The etiology of OS remains multifactorial, involving genetic predispositions, environmental exposures, and complex molecular alterations. Despite advances in surgery and chemotherapy, therapeutic outcomes remain suboptimal due to the high propensity for metastasis and chemoresistance. This review explores recent insights into the genomic landscape of OS, with a focus on the regulatory roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in tumor initiation, progression, and therapy resistance. We further examine emerging strategies that target these non-coding RNAs as potential therapeutic agents or biomarkers for diagnosis and prognosis. Ultimately, this review emphasizes the need for innovative RNA-based approaches to improve the clinical management and survival outcomes of osteosarcoma patients.