Cancer remains one of the leading causes of morbidity and mortality worldwide, characterized by profound molecular heterogeneity and adaptive capacity [1]. The transition from conventional cytotoxic approaches to targeted, precision-based therapies has significantly improved clinical outcomes [2]. However, therapeutic resistance and tumor plasticity continue to limit long-term success. Therefore, identifying and validating new anticancer targets, spanning genetic, epigenetic, metabolic, and microenvironmental layers, remains a central challenge in contemporary oncology.

This Special Issue, “New Targets in Anticancer Therapy”, brings together original research and review articles addressing emerging targets and mechanisms across key areas, including precision medicine, immuno-oncology, DNA damage response, metabolic regulation, and gene-targeting strategies. Collectively, these contributions emphasize that cancer progression and therapeutic response are governed by interconnected biological systems, requiring integrative, context-dependent therapeutic approaches.

A growing body of evidence highlights the importance of tumor-microenvironment interactions in shaping therapeutic outcomes. He et al. [3] provide a comprehensive overview of tumor-associated macrophages (TAMs) in breast cancer, emphasizing their dual role in tumor progression and immune modulation. The authors discuss strategies to reprogram TAMs toward anti-tumor phenotypes, underscoring their potential as immunotherapeutic targets. Complementing this perspective, Sinanian et al. [4] explore the mechanisms of action of Sacituzumab Govitecan, an antibody–drug conjugate, demonstrating how its efficacy extends beyond cytotoxicity to involve autophagy, senescence, and immune system engagement. These findings highlight the complexity of therapeutic responses and the need to consider network-level effects rather than isolated pathways.

Metabolic reprogramming has emerged as a hallmark of cancer and a promising source of novel targets. Chen et al. [5] investigate phosphoglycerate kinase 1 (PGK1) in esophageal squamous cell carcinoma and demonstrate that its inhibition enhances radiosensitivity to both X-rays and carbon ion irradiation. This study provides compelling evidence that targeting metabolic enzymes can modulate treatment response and overcome radioresistance. Ying et al. [6] employ comparative proteomic analysis to characterize irradiation-induced radioresistant breast cancer cells, identifying protein networks associated with adaptive resistance. Together, these studies underscore the importance of systems-level approaches in understanding and targeting resistance to therapy.

Advances in molecular targeting have also expanded into previously underexplored regulatory areas. Chanda et al. [7] demonstrate that the RNA-binding protein IGF2BP2/IMP2 is functionally essential for cancer cell survival, as its genetic disruption impairs proliferation, migration, and tumorigenic capacity. Importantly, pharmacological inhibition recapitulates these effects, validating IMP2 as a druggable post-transcriptional regulator and a promising anticancer target. Similarly, Zheng et al. [8] identify LINC01572 as a novel prognostic biomarker and therapeutic target in lung adenocarcinoma, further supporting the relevance of long non-coding RNAs in cancer biology. These findings illustrate how non-coding and RNA-regulatory mechanisms are increasingly recognized as actionable targets.

Targeting oncogenic signalling pathways remains a cornerstone of anticancer therapy. Kumar et al. [9] apply an e-pharmacophore-based virtual screening and drug repurposing approach to identify potential inhibitors of KRAS-driven cancers, addressing one of the most challenging targets in oncology. Their work demonstrates how computational and structural strategies can accelerate the discovery of novel therapeutics and the repurposing of existing compounds.

Finally, Zhang et al. [10] review gemcitabine-based chemosensitization strategies in pancreatic ductal adenocarcinoma, highlighting approaches to enhance the efficacy of conventional chemotherapy through targeted combinations. This contribution emphasizes that the development of new targets does not replace established therapies but rather refines and potentiates them within integrated treatment regimens.

Taken together, the articles in this Special Issue converge on several key themes. First, cancer is a dynamic and adaptive system in which resistance mechanisms are intrinsic and multifactorial. Second, effective targeting strategies must extend beyond single molecules to encompass regulatory networks, cellular states, and microenvironmental interactions. Third, combinatorial and precision-based approaches are essential to translate molecular insights into durable clinical benefits.

In summary, “New Targets in Anticancer Therapy” highlights the expanding landscape of actionable vulnerabilities in cancer, from metabolic enzymes and RNA regulators to immune components and signaling pathways. By integrating insights from diverse disciplines, this Special Issue provides a comprehensive perspective on emerging therapeutic strategies and underscores the importance of systems-level thinking in the development of next-generation anticancer therapies.

Author Contributions

The single author was responsible for the entire preparation of this manuscript.

Ethics Approval and Consent to Participate

Not applicable.

Acknowledgment

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Funding

This research received no external funding.

Conflicts of Interest

Given her role as the Guest Editor, Milena Georgieva had no involvement in the peer-review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Graham Pawelec.