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Rapid advances in molecular oncology, multi-omics profiling, and high-resolution tumour mapping continue to reshape our understanding of cancer initiation, progression, and therapeutic resistance. As cancer remains a major global health burden, the identification of novel molecular targets has become central to the development of precise, durable, and context-specific interventions. The Research Topic Novel Molecular Targets in Cancer Therapy provides a dedicated platform for showcasing emerging biomarkers, mechanistic discoveries, translational targets, and early-stage therapeutic strategies across diverse malignancies. The articles collected here collectively illustrate how integrative molecular approaches can uncover actionable vulnerabilities, thereby refining prognostic and therapeutic frameworks. A major focus of this Research Topic is the use of genomic and transcriptomic tools to identify biomarkers that not only predict clinical outcomes but may also serve as direct therapeutic targets. In colorectal cancer liver metastasis, a comprehensive single-cell transcriptomic study constructed a prognostic model and dissected macrophage migration inhibitory factor (MIF)-related signalling, revealing cellular heterogeneity and regulatory dependencies that may guide personalized therapy (doi: 10.3389/fonc.2025.1588514). Downregulation of SALL1 in clear cell renal cell carcinoma was found to correlate with poor prognosis and alterations in the immune cell landscape, suggesting that SALL1 may have dual relevance as both a prognostic biomarker and a modulator of tumour-immune interactions( doi: 10.3389/fonc.2025.1624651).Expanding beyond tumour-specific analysis, a pan-cancer study of SLC7A11 highlighted its prognostic significance in hepatocellular carcinoma and reinforced the therapeutic importance of redox regulation, as elevated SLC7A11 expression was linked to adverse clinical outcomes (doi: 10.3389/fonc.2025.1601140). In glioblastoma, MEX3A was identified as a diagnostic and independent prognostic biomarker, offering a promising foundation for therapeutic targeting in one of the most treatment-resistant cancers (doi: 10.3389/fonc.2025.1585592). Together, these contributions emphasize the value of molecular stratification in exposing targetable liabilities and improving outcome prediction. Beyond identifying individual prognostic biomarkers, this Research Topic highlights mechanistic and systems-level approaches for molecular subtyping and immune-related therapeutic discovery. For instance, in Wilms tumour, a study integrating immune gene signatures delineated NK cell-associated molecular subtypes. This approach not only revealed prognostic differences but also nominatedHS2ST1 as a potential biomarker. Significantly, the work identified TGX-221 as a potent candidate therapeutic agent for patients with poor survival signatures, underscoring the direct translational impact of this immune-driven molecular classification (doi: 10.3389/fonc.2025.1593011).These findings align with the growing recognition that the tumour immune microenvironment is integral not only to cancer progression but also to therapy responsiveness. By leveraging immune-related transcriptional markers, the study provides a framework for refining immunotherapeutic strategies in paediatric renal cancers. Research Topic underscore a central theme: the future of cancer therapy will rely on three pillars: molecular precision, therapeutic diversification, and integration of multi-omics approaches. Whether through identifying prognostic biomarkers, defining immune-related subtypes, or uncovering novel regulatory pathways such as glycosylation networks progress in oncology increasingly depends on detailed mechanistic insight coupled with translational rigor. These contributions highlight the expanding repertoire of potential therapeutic targets and reinforce the importance of systems-level investigation in refining precision oncology.We extend our sincere appreciation to all authors, reviewers, and contributors for their engagement and scientific commitment. The discoveries highlighted in this collection broaden the current understanding of molecular targets in cancer and support ongoing efforts to develop the next generation of individualized, effective cancer therapies.The Novel Molecular Targets in Cancer Therapy Research Topic offers a robust snapshot of contemporary efforts to refine and expand molecularly guided cancer treatment. The breadth of contributions from biomarker identification and prognostic modelling to clinical translation and therapeutic review demonstrates both the progress made and the challenges ahead in targeting cancer at the molecular level. We thank all authors and reviewers for their valuable contributions, which collectively advance the field toward more precise, effective, and personalized cancer therapies.