Radiogenomics is an emerging field that integrates genomic data with radiological imaging to enhance personalized therapy in cancer treatment. A pivotal study demonstrated that germline loss-of-function variants in ELP1 are prevalent in childhood medulloblastoma, particularly in the Sonic hedgehog subtype, suggesting that targeting MDM2 could be a selective therapeutic strategy (ref: Ahmad doi.org/10.1016/j.ccell.2025.04.014/). In osteosarcoma, a kinome-wide CRISPR screen identified PKMYT1 as a key regulator of cisplatin sensitivity, highlighting the potential for targeted therapies to overcome chemoresistance (ref: Liu doi.org/10.1038/s41392-025-02250-7/). The TOPAZ-1 study further supports this theme by showing that durvalumab combined with chemotherapy significantly improves overall survival in advanced biliary tract cancer, emphasizing the importance of integrating immunotherapy with traditional chemotherapy (ref: Oh doi.org/10.1016/j.jhep.2025.05.003/). Additionally, the efficacy of patritumab deruxtecan in treating leptomeningeal metastatic disease showcases the potential of antibody-drug conjugates in targeting specific cancer types (ref: Preusser doi.org/10.1038/s41591-025-03744-1/). The development of a radiogenomics prognostic model for non-small cell lung cancer, which integrates PET/CT radiomics and glucose metabolism-related gene signatures, further illustrates the potential for personalized treatment strategies based on individual tumor characteristics (ref: Wang doi.org/10.1007/s00259-025-07354-4/).

The tumor microenvironment (TME) plays a critical role in cancer progression and therapy resistance. A study on prostate cancer revealed that CHD1 loss reprograms cholesterol synthesis, fueling androgen-responsive growth and contributing to castration resistance (ref: Chen doi.org/10.1038/s43018-025-00952-z/). In non-small cell lung cancer, impaired T cell and neoantigen retention was observed in patients unresponsive to tumor-infiltrating lymphocyte therapy, indicating that TME alterations can hinder effective immunotherapy (ref: Wang doi.org/10.1038/s43018-025-00946-x/). Innovative approaches such as in situ magnetoelectric generation of miRNA sponges have been developed to enhance nerve regeneration, demonstrating the potential for electrical stimulation in modulating TME responses (ref: Pan doi.org/10.1002/adma.202500650/). Furthermore, GP73-dependent regulation of exosome biogenesis was shown to promote colorectal cancer liver metastasis, highlighting the importance of exosomal communication in TME dynamics (ref: Huang doi.org/10.1186/s12943-025-02350-6/). The inhibition of CD47 via USP2 has been shown to enhance anti-tumor immunity by unleashing phagocytosis, indicating that targeting immune checkpoints can effectively modulate the TME (ref: Dai doi.org/10.1038/s41467-025-59621-5/).

Understanding the mechanisms of resistance to therapy is crucial for improving cancer treatment outcomes. A significant finding revealed that APOBEC3 mutagenesis drives therapy resistance in breast cancer, with whole-genome sequencing showing that this process leads to genetic alterations such as RB1 loss (ref: Gupta doi.org/10.1038/s41588-025-02187-1/). In multiple myeloma, a phase 1 trial of BCMA/GPRC5D bispecific CAR T-cell therapy demonstrated promising results in patients with extramedullary disease, suggesting that novel immunotherapies can overcome traditional resistance mechanisms (ref: Yao doi.org/10.1186/s13045-025-01713-2/). Additionally, the study of CSDE1 revealed its role in enhancing resistance to genotoxic drugs by modulating DNA repair pathways, indicating that targeting such pathways could reverse resistance (ref: Cui doi.org/10.1016/j.drup.2025.101249/). Furthermore, mutant p53 was shown to confer chemoresistance in nasopharyngeal carcinoma by activating DNA repair pathways, highlighting the need for therapies that can target these mutations (ref: Luo doi.org/10.1016/j.canlet.2025.217736/). The exploration of ferroptosis as a therapeutic strategy in colorectal cancer also underscores the importance of understanding resistance mechanisms, with the selenoproteome identified as a potential target (ref: DeAngelo doi.org/10.1158/0008-5472.CAN-24-3478/).

Innovative therapeutic strategies are essential for addressing the challenges posed by various cancers. Focused ultrasound-microbubble treatment has shown promise in controlling the growth of cerebral cavernous malformations, offering a non-invasive alternative to traditional surgical methods (ref: Fisher doi.org/10.1038/s41551-025-01390-z/). In serous endometrial carcinoma, the combination of rucaparib and PLX038A demonstrated significant antitumor activity in patient-derived xenografts, indicating the potential for novel drug combinations to improve treatment outcomes (ref: Hou doi.org/10.1186/s13046-025-03406-7/). Additionally, the knockdown of ITGB3 was found to enhance radiosensitivity in osteosarcoma, linking osteogenic differentiation to improved therapeutic responses (ref: Lian doi.org/10.1186/s13046-025-03417-4/). The development of deep learning tools like Deep scSTAR for extracting phenotype-associated features from single-cell RNA sequencing data represents a significant advancement in understanding tumor biology and tailoring therapies (ref: Gao doi.org/10.1093/bib/). Moreover, the use of nanovaccines for inducing immune tolerance in rheumatoid arthritis highlights the versatility of innovative strategies in treating various conditions (ref: Cao doi.org/10.1016/j.jconrel.2025.113842/).

Genetic and epigenetic factors significantly influence cancer development and treatment responses. A comprehensive study of classic Hodgkin lymphoma using circulating tumor DNA revealed critical insights into the genetic landscape of this malignancy, particularly the role of BCL6 in gene repression (ref: Pirosa doi.org/10.1182/blood.2024027355/). The genomic landscape of gastric cancer was further elucidated through the comparison of primary and peritoneal metastatic lesions, highlighting the evolutionary dynamics and mutational drivers involved in cancer progression (ref: Li doi.org/10.1016/j.jare.2025.05.043/). Additionally, the targeting of the innate immune checkpoint TREX1 has emerged as a promising immunotherapeutic strategy, demonstrating the potential for genetic manipulation to enhance anti-tumor immunity (ref: Xing doi.org/10.1158/0008-5472.CAN-24-2747/). The development of 68Ga-NK224 PET/CT for noninvasive evaluation of PD-L1 expression underscores the importance of imaging technologies in assessing tumor heterogeneity and guiding treatment decisions (ref: Zhao doi.org/10.1158/1078-0432.CCR-25-0160/). Moreover, the reactivation of cGAS-STING signaling through SOS1 inhibition has been shown to enhance antitumor immunity, indicating that genetic pathways can be targeted to improve therapeutic efficacy (ref: Shan doi.org/10.1158/0008-5472.CAN-24-2983/).

Clinical trials play a crucial role in evaluating new treatment strategies and their outcomes. The CTC1-STN1-TEN1 complex was shown to control DNA break repair pathway choice, providing insights into the mechanisms underlying treatment responses and resistance (ref: Rogers doi.org/10.1126/science.adt3034/). A study on radiosensitizing the SUMO stress response demonstrated that combining antiangiogenic drugs with single-dose radiotherapy could enhance tumor cure rates, suggesting a novel approach to improve radiotherapy outcomes (ref: Cheng doi.org/10.1172/jci.insight.153601/). The role of long non-coding RNAs in enhancing radiosensitivity was highlighted by the discovery of WDR11-DT, which promotes homologous recombination deficiency (ref: Yang doi.org/10.1016/j.canlet.2025.217757/). Furthermore, innovative delivery systems for siRNA targeting immunosuppressive signals in gliomas have shown promise in overcoming the challenges posed by the tumor microenvironment (ref: Li doi.org/10.1021/acsnano.4c11892/). The exploration of GP73's role in colorectal cancer liver metastasis emphasizes the need for understanding molecular pathways to improve treatment strategies (ref: Huang doi.org/10.1186/s12943-025-02350-6/).

Radiotherapy remains a cornerstone in cancer treatment, yet resistance mechanisms significantly limit its efficacy. Research has shown that hypoxia-induced radioresistance is a major factor contributing to treatment failure, with studies indicating that cholesterol biosynthesis induced by radiotherapy inhibits cGAS-STING activation, leading to colorectal cancer treatment resistance (ref: Zhu doi.org/10.1038/s12276-025-01457-6/). The development of nitrobenzene-functionalized gold nanoparticles aims to enhance radiotherapy effectiveness by overcoming hypoxia-related challenges (ref: Zhao doi.org/10.1002/anie.202504524/). Moreover, the integration of cGAS-STING signaling reactivation through SOS1 inhibitors has been shown to enhance antitumor immunity in NRAS-mutant tumors, indicating a potential strategy to counteract radiotherapy resistance (ref: Shan doi.org/10.1158/0008-5472.CAN-24-2983/). The use of mesoporous materials in antimicrobial photodynamic therapy also highlights innovative approaches to enhance treatment efficacy in the context of biofilm-related infections (ref: Li doi.org/10.1002/adhm.202500964/). Additionally, the mutagenic impact of chemoradiotherapy in hematologic malignancies underscores the need for comprehensive strategies to manage treatment-related genetic alterations (ref: Diamond doi.org/10.1158/2643-3230.BCD-24-0328/).

Emerging biomarkers and diagnostic tools are crucial for advancing cancer treatment and monitoring. The recharacterization of the tumor suppressive mechanism of RSL3 has identified the selenoproteome as a potential druggable pathway in colorectal cancer, emphasizing the importance of targeting metabolic pathways in cancer therapy (ref: DeAngelo doi.org/10.1158/0008-5472.CAN-24-3478/). The combination of multiplexed CRISPR/Cas9-nickase and PARP inhibitors has shown promise in precisely targeting cancer cells, highlighting the potential of genetic engineering in improving therapeutic outcomes (ref: Lee doi.org/10.1158/0008-5472.CAN-24-2938/). Additionally, the reactivation of cGAS-STING signaling through SOS1 inhibitors has been demonstrated to enhance antitumor immunity, indicating the potential for novel therapeutic strategies that leverage immune pathways (ref: Shan doi.org/10.1158/0008-5472.CAN-24-2983/). The development of conductive granular scaffolds for targeted miRNA regulation in nerve repair represents a significant advancement in non-viral gene modulation techniques (ref: Pan doi.org/10.1002/adma.202500650/). Furthermore, the role of long non-coding RNAs in enhancing radiosensitivity in non-small cell lung cancer underscores the potential for utilizing genetic markers to guide treatment decisions (ref: Yang doi.org/10.1016/j.canlet.2025.217757/).