Recent studies have explored the interactions between radiotherapy and immunotherapy, particularly in the context of triple-negative breast cancer (TNBC). Shiao et al. utilized single-cell transcriptomics and spatial proteomics to analyze TNBC biopsies at various treatment stages, revealing that non-responders to pembrolizumab exhibited a lack of immune infiltrate and minimal immune changes post-therapy (ref: Shiao doi.org/10.1016/j.ccell.2023.12.012/). Complementarily, Shaitelman et al. highlighted the synergy between radiotherapy and pembrolizumab, suggesting that microenvironment-guided patient selection could enhance treatment efficacy (ref: Shaitelman doi.org/10.1016/j.ccell.2023.12.009/). In the realm of lung cancer, Memon et al. identified mechanisms of acquired resistance to PD-(L)1 blockade, emphasizing the role of persistent IFN signaling and immune dysfunction, which could inform strategies to overcome resistance (ref: Memon doi.org/10.1016/j.ccell.2023.12.013/). These findings collectively underscore the importance of understanding tumor microenvironments and immune responses in optimizing combined treatment modalities.

The mechanisms underlying radioresistance have been a focal point of recent research, particularly regarding the role of ferroptosis and epigenetic reprogramming. Lin et al. demonstrated that acquired radioresistance in cancer cells is linked to a shift in ferroptosis dependence from GPX4 to FSP1, indicating a potential therapeutic target for overcoming resistance (ref: Lin doi.org/10.1016/j.drup.2023.101032/). Jiang et al. further explored cervical cancer, revealing that TRAIL-driven targeting can reverse radioresistance by modulating cell metabolism, highlighting the potential of metabolic interventions in enhancing radiosensitivity (ref: Jiang doi.org/10.1016/j.drup.2023.101033/). Additionally, Liu et al. provided insights into the epigenetic landscape of schwannomas, suggesting that distinct molecular groups influence tumor cell states and responses to therapy (ref: Liu doi.org/10.1038/s41467-023-40408-5/). These studies illustrate the multifaceted nature of radioresistance and the need for innovative strategies to enhance treatment efficacy.

The tumor microenvironment (TME) plays a critical role in cancer progression and treatment response, as evidenced by recent studies focusing on pancreatic ductal adenocarcinoma (PDAC) and immune checkpoint inhibitors (ICIs). George et al. developed a transcriptomic profiling platform that classifies the TME based on functional gene signatures, which could lead to more precise therapeutic strategies for PDAC (ref: George doi.org/10.1053/j.gastro.2024.01.028/). Wang et al. examined the KMT2 family mutations and their association with ICI therapy, revealing that epigenetic regulation significantly impacts tumor immunity and treatment outcomes (ref: Wang doi.org/10.1186/s12943-023-01930-8/). Furthermore, Flies et al. assessed treatment-associated imaging changes in glioblastoma, emphasizing the complexities of radiological progression and the implications for treatment strategies (ref: Flies doi.org/10.1093/neuonc/). These findings highlight the intricate interplay between genomic factors and the TME in shaping cancer therapy responses.

Epigenetic regulation has emerged as a pivotal factor in cancer therapy, influencing treatment responses and resistance mechanisms. Liu et al. identified germline-specific genes that enhance DNA double-strand break repair and contribute to radioresistance in lung adenocarcinoma cells, suggesting that targeting these pathways may improve therapeutic outcomes (ref: Liu doi.org/10.1038/s41419-024-06433-y/). Additionally, the study by Li et al. on a self-cascade nanozyme reactor demonstrated how cuproptosis induction can synergistically enhance radioimmunotherapy by improving tumor oxygenation and promoting cell death (ref: Li doi.org/10.1002/smll.202306263/). Geng et al. further elucidated the role of transketolase in DNA repair mechanisms, linking it to radioresistance in hepatocellular carcinoma (ref: Geng doi.org/10.1038/s41388-023-02935-9/). Collectively, these studies underscore the potential of epigenetic modulation as a therapeutic strategy to overcome resistance and enhance the efficacy of cancer treatments.

Innovative therapeutic strategies are being developed to enhance treatment efficacy and overcome resistance in various cancers. Nassar et al. conducted a multicenter retrospective study comparing consolidation therapies after chemoradiation in EGFR-mutant non-small cell lung cancer (NSCLC), revealing that osimertinib may offer comparable outcomes to durvalumab (ref: Nassar doi.org/10.1016/j.jtho.2024.01.012/). Concurrently, Zhang et al. highlighted the role of KDM5B in promoting tumor progression and cisplatin resistance in nasopharyngeal carcinoma, suggesting that targeting this pathway could reverse resistance (ref: Zhang doi.org/10.1038/s41418-024-01257-x/). Furthermore, Wang et al. introduced a nanoplatform that enhances photodynamic therapy against osteosarcoma by inducing ferroptosis and alleviating hypoxia, showcasing the potential of nanotechnology in cancer treatment (ref: Wang doi.org/10.1002/smll.202306916/). These advancements reflect a growing emphasis on personalized and targeted therapies in oncology.

The identification of biomarkers and the development of predictive models are crucial for optimizing cancer treatment strategies. Liu et al. introduced a deep neural network model to predict sensitivity to neoadjuvant chemoradiotherapy in locally advanced rectal cancer, utilizing transcriptomic profiles to enhance clinical decision-making (ref: Liu doi.org/10.1016/j.canlet.2024.216641/). Flies et al. also contributed to this field by analyzing treatment-associated imaging changes in glioblastoma, which could inform the differentiation between true progression and pseudoprogression (ref: Flies doi.org/10.1093/neuonc/). Additionally, Marquez-Palencia et al. explored the role of AXL/WRNIP1 in mediating replication stress response and therapy resistance in HER2+ breast cancer, providing insights into potential therapeutic targets (ref: Marquez-Palencia doi.org/10.1158/0008-5472.CAN-23-1459/). These studies highlight the importance of integrating biomarker discovery with predictive modeling to enhance treatment outcomes.

Clinical trials continue to shape the landscape of cancer treatment, with recent guidelines and studies providing critical insights into treatment outcomes. The Chinese Society of Clinical Oncology updated its clinical guidelines for gastric cancer, emphasizing the need for evidence-based practices tailored to the unique characteristics of Eastern and Western populations (ref: Wang doi.org/10.1002/cac2.12516/). Alaeikhanehshir et al. evaluated the risk factors for locoregional breast cancer recurrence, finding an 8-year cumulative incidence of 3.2%, which underscores the importance of genetic profiling in predicting recurrence risk (ref: Alaeikhanehshir doi.org/10.1200/JCO.22.02690/). Additionally, Burlile et al. analyzed patterns of progression after immune checkpoint inhibitors in Hodgkin lymphoma, revealing that a significant proportion of patients experienced progression at pre-treatment sites, which has implications for radiation therapy strategies (ref: Burlile doi.org/10.1182/bloodadvances.2023011533/). These findings reflect the ongoing evolution of clinical practice informed by rigorous research.