The theme of radiogenomics and treatment resistance explores the complex interplay between genetic factors and therapeutic outcomes in cancer treatment. One significant study introduced the RECODR pipeline, which utilizes co-expression graph networks from single-cell RNA sequencing to identify changes in gene co-expression context during cancer treatment. This approach revealed that understanding gene context drift can uncover potential drug targets to mitigate treatment resistance, emphasizing the importance of gene co-expression over mere expression levels (ref: Jassim doi.org/10.1016/j.ccell.2025.06.005/). In cervical cancer, the CALLA trial analyzed the role of circulating tumor DNA (ctDNA) and human papillomavirus (HPV) DNA as prognostic biomarkers, finding that ultrasensitive detection of ctDNA could predict relapse and survival in patients post-chemoradiotherapy, despite the overall treatment not significantly improving progression-free survival (ref: Mayadev doi.org/10.1016/j.annonc.2025.05.533/). Furthermore, research on triple-negative breast cancer (TNBC) highlighted the role of ENPP1 in promoting treatment resistance through its involvement in DNA damage repair mechanisms, suggesting that dual depletion of ENPP1 and ATM could enhance the efficacy of radioimmunotherapy (ref: Ruiz-Fernández de Córdoba doi.org/10.1038/s41392-025-02271-2/). These studies collectively underscore the necessity of integrating genomic insights into therapeutic strategies to overcome resistance in various cancer types.

Research on cardiotoxicity and long-term effects of cancer treatment has highlighted the significant risks faced by childhood cancer survivors. A pivotal study developed a risk prediction model for cardiomyopathy in this population, utilizing data from the St. Jude Lifetime Cohort and the Childhood Cancer Survivor Study. The model demonstrated high performance in estimating the 10-year risk of cardiomyopathy, emphasizing the need for ongoing cardiovascular monitoring in survivors (ref: Petrykey doi.org/10.1016/j.annonc.2025.05.539/). Additionally, another study assessed the contributions of cancer treatment and genetic predisposition to the risk of subsequent neoplasms in childhood cancer survivors, revealing that both factors play critical roles in the development of secondary cancers, while lifestyle factors had minimal impact (ref: Neupane doi.org/10.1016/S1470-2045(25)00157-3/). These findings highlight the importance of long-term follow-up and tailored surveillance strategies to address the unique health challenges faced by this vulnerable population.

The theme of immunotherapy and immune microenvironment modulation focuses on the interactions between immune cells and tumor environments that influence treatment efficacy. A study revealed that tumor-associated NK cells can hinder CD8+ T-cell differentiation by competing for critical cytokines, thereby contributing to resistance against immune checkpoint blockers (ref: Song doi.org/10.1158/2159-8290.CD-24-1232/). Another investigation into the effects of neoadjuvant radiotherapy combined with immune checkpoint blockade in undifferentiated pleomorphic sarcoma found that the ICB group exhibited significantly greater tumor hyalinization, suggesting enhanced immune infiltration and potential therapeutic benefits (ref: Traweek doi.org/10.1016/j.esmoop.2025.105493/). Furthermore, research on the role of FGFR3-induced PARP1 phosphorylation in breast cancer models indicated that this modification promotes resistance to PARP inhibitors, highlighting the potential for combining FGFR inhibitors with PARP inhibitors to restore treatment efficacy (ref: Chen doi.org/10.1172/JCI173757/). These studies collectively underscore the intricate dynamics of the immune microenvironment and its implications for improving immunotherapeutic strategies.

Nanotechnology has emerged as a transformative approach in cancer therapy, particularly in enhancing the efficacy of existing treatments. One study developed an organic AIE nanoradiosensitizer that significantly improves the generation of reactive oxygen species (ROS) during radiotherapy, thereby potentiating cancer radioimmunotherapy (ref: Xu doi.org/10.1002/adma.202502898/). Another investigation introduced a multifunctional anisotropic gold-palladium nanosystem designed to overcome radioresistance in melanoma, demonstrating enhanced systemic antitumor immunity through improved DNA damage responses (ref: Chen doi.org/10.1002/advs.202500492/). Additionally, research on low-dose photodynamic therapy (PDT) indicated that it promotes vascular E-selectin expression, facilitating immune cell recruitment and improving tumor control in chest malignancies (ref: Chriqui doi.org/10.1136/jitc-2024-009482/). These advancements highlight the potential of nanotechnology to address critical challenges in cancer treatment, including resistance and immune evasion.

Recent advancements in radiotherapy techniques have focused on optimizing treatment efficacy and minimizing adverse effects. A phase 3 trial compared induction versus adjuvant chemoradiotherapy in high-risk nasopharyngeal carcinoma, revealing comparable safety profiles but differing efficacy outcomes, with notable adverse events such as leukopenia and mucositis observed in both groups (ref: Guo doi.org/10.1001/jamaoncol.2025.1597/). Another study evaluated stereotactic body radiation therapy (SBRT) for primary renal cancer, identifying genomic predictors of response and demonstrating its impact on renal function in surgically unfit patients (ref: Song doi.org/10.1016/j.euo.2025.06.001/). Furthermore, research on the combination of radiation and local cisplatin release for head and neck cancer treatment highlighted the potential for improved therapeutic outcomes while addressing systemic toxicity concerns (ref: Daher-Ghanem doi.org/10.1016/j.jconrel.2025.113923/). These findings underscore the importance of refining radiotherapy techniques to enhance patient outcomes and reduce long-term complications.

The exploration of genomic and epigenetic factors in cancer has provided insights into tumor biology and treatment responses. A study on skull base chordoma utilized radiogenomics to classify novel radiomic subgroups and predict genetic signatures, revealing the aggressive nature of these tumors and their resistance to conventional therapies (ref: Gersey doi.org/10.1093/neuonc/). Another investigation into the role of FTSJ3 in lung cancer demonstrated that its loss promotes R-loop-associated DNA damage, sensitizing cells to chemotherapy, which highlights the potential for targeting such epigenetic factors in therapeutic strategies (ref: Chen doi.org/10.1016/j.canlet.2025.217877/). Additionally, research on central neurocytoma identified global DNA hypomethylation as a hallmark feature associated with higher recurrence risk, emphasizing the need for molecularly informed risk stratification in clinical practice (ref: Krech doi.org/10.1007/s00401-025-02894-3/). These studies collectively illustrate the critical role of genomic and epigenetic alterations in shaping cancer behavior and treatment outcomes.

Targeted therapies and personalized medicine have revolutionized cancer treatment by tailoring interventions to individual patient profiles. A phase II trial of transoral surgery combined with risk-based adjuvant treatment for HPV-associated oropharynx cancer demonstrated high progression-free and overall survival rates, underscoring the effectiveness of deintensified postoperative management (ref: Burtness doi.org/10.1200/JCO-24-02550/). In the context of metastatic non-small-cell lung cancer, the GEMSTONE-302 trial revealed that the addition of sugemalimab to platinum-based chemotherapy significantly improved progression-free and overall survival compared to placebo (ref: Zhou doi.org/10.1016/S1470-2045(25)00198-6/). Furthermore, the PHAROS study highlighted the robust antitumor activity of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic NSCLC, demonstrating the potential of targeted therapies to achieve durable responses (ref: Riely doi.org/10.1016/j.jtho.2025.05.023/). These findings emphasize the importance of integrating biomarker-driven approaches into clinical practice to enhance treatment efficacy and patient outcomes.

Emerging biomarkers and prognostic models are crucial for improving cancer treatment outcomes and personalizing therapy. One study identified CART cell senescence as a resistance mechanism in 41BB-costimulated CART cell therapy, suggesting that senescence signatures could serve as biomarkers for predicting treatment responses (ref: Can doi.org/10.1186/s12943-025-02371-1/). Additionally, research on nuclear deformability indicated that it increases PARP inhibitor sensitivity in BRCA1-deficient cells, highlighting the potential for using nuclear structure as a prognostic factor in treatment planning (ref: Faustini doi.org/10.1038/s41467-025-60756-8/). Furthermore, a radiomics-based unsupervised clustering study in clear cell renal cell carcinoma revealed distinct subtypes associated with prognosis and immune microenvironment, paving the way for improved risk stratification in clinical settings (ref: Guo doi.org/10.1002/advs.202506165/). These studies collectively underscore the importance of identifying and validating new biomarkers to enhance prognostic accuracy and inform therapeutic decisions.