The tumor microenvironment (TME) plays a critical role in shaping the immune response to cancer therapies. Recent studies have highlighted the importance of myeloid cell reprogramming in enhancing anti-tumor immunity. For instance, Liu et al. demonstrated that CD11b agonists can activate STING-interferon signaling, leading to a shift in tumor-associated macrophage (TAM) phenotypes by repressing NF-κB signaling while simultaneously activating interferon gene expression (ref: Liu doi.org/10.1016/j.ccell.2023.04.018/). This dual action suggests a promising therapeutic strategy to overcome the immunosuppressive nature of tumors. Additionally, Chang et al. introduced a novel method for synthesizing Se/Te nanochaperones that enhance cancer radio-immunotherapy, addressing the challenges of radiotherapy by improving the efficacy of treatment through engineered nanostructures (ref: Chang doi.org/10.1002/adma.202212178/). Furthermore, the genomic profiling of radiation-induced sarcomas (RIS) revealed their immunologic characteristics and response to immune checkpoint blockade, indicating that RIS may benefit from targeted immunotherapy strategies (ref: Hong doi.org/10.1158/1078-0432.CCR-22-3567/). These findings collectively underscore the potential of manipulating the TME to improve therapeutic outcomes in cancer treatment. Moreover, the interplay between the TME and immune response is further illustrated in studies focusing on specific cancer types. For example, Mondal et al. found that the deficiency of PP2Ac in glioblastoma cells enhances tumor immunogenicity by activating STING-type I interferon signaling, which could provide a new avenue for immunotherapy in otherwise resistant tumors (ref: Mondal doi.org/10.1158/0008-5472.CAN-22-3382/). Similarly, Li et al. developed an artificial exosome-constructed hydrogel aimed at targeting peritoneal macrophages for ovarian cancer therapy, showcasing an innovative approach to harnessing the immune system for localized treatment (ref: Li doi.org/10.1021/acsnano.3c00804/). Overall, these studies highlight the critical role of the TME in influencing therapeutic responses and the ongoing efforts to exploit these interactions for improved cancer therapies.

Genomic profiling has emerged as a cornerstone of personalized medicine, particularly in the context of metastatic castration-sensitive prostate cancer (mCSPC). Sutera et al. explored the transcriptomic and clinical heterogeneity of metastatic disease timing, revealing significant differences in biological behavior and treatment responses between synchronous and metachronous mCSPC (ref: Sutera doi.org/10.1016/j.annonc.2023.04.515/). This study emphasizes the need for tailored therapeutic strategies based on the timing of metastasis, which could inform clinical decision-making. Additionally, another study by Sutera et al. compared clinical and genomic differences between advanced molecular imaging-detected and conventional imaging-detected oligometastatic mCSPC, highlighting the implications of imaging modalities on treatment approaches (ref: Sutera doi.org/10.1016/j.eururo.2023.04.025/). These findings suggest that advanced imaging techniques may provide critical insights into disease progression and treatment efficacy. Furthermore, comprehensive genomic profiling across ancestries in advanced prostate cancer revealed that while ancestry-specific mutational landscapes exist, the prevalence of alterations in actionable genes remained consistent across different populations (ref: Sivakumar doi.org/10.1016/S2589-7500(23)00053-5/). This underscores the importance of considering genetic diversity in developing targeted therapies. In the context of gliomas, Kinslow et al. investigated the association of MGMT promoter methylation with survival outcomes after alkylating chemotherapy, suggesting that this biomarker could serve as a stratification factor in clinical trials (ref: Kinslow doi.org/10.1001/jamaoncol.2023.0990/). Collectively, these studies highlight the potential of genomic profiling to inform personalized treatment strategies and improve patient outcomes in cancer care.

Radiotherapy remains a cornerstone of cancer treatment, yet resistance to radiation therapy poses significant challenges. Recent research has focused on understanding the mechanisms underlying radiosensitivity and developing strategies to enhance the efficacy of radiotherapy. Floyd et al. demonstrated that ATRX deletion impairs CGAS/STING signaling, leading to increased sensitivity of sarcomas to radiation and oncolytic herpesvirus therapy (ref: Floyd doi.org/10.1172/JCI149310/). This finding suggests that targeting ATRX could be a viable strategy to improve treatment outcomes in sarcoma patients. Additionally, Zeng et al. introduced a metal-organic framework (MOF)-based ferroptosis inducer that enhances radiotherapy for triple-negative breast cancer, highlighting the potential of combining ferroptosis induction with radiation to overcome resistance (ref: Zeng doi.org/10.1021/acsnano.3c00048/). Moreover, Xie et al. explored the effects of E-cadherin gene delivery during specific cell cycle phases, revealing that targeting the G2/M phase significantly enhances tumor invasion and metastasis inhibition (ref: Xie doi.org/10.1038/s41392-023-01398-4/). This innovative approach underscores the importance of timing in gene therapy applications. In colorectal cancer, Xie et al. also investigated the role of APR-246 in enhancing sensitivity to radiotherapy, particularly in tumors with mutant p53, suggesting that restoring p53 function could improve treatment responses (ref: Xie doi.org/10.1158/1535-7163.MCT-22-0275/). These studies collectively highlight the ongoing efforts to understand and manipulate radiosensitivity mechanisms to improve therapeutic outcomes in cancer treatment.

Understanding the biological mechanisms underlying cancer resistance is crucial for developing effective therapies. Recent studies have shed light on various factors contributing to resistance, particularly in the context of radiation and chemotherapy. Hosseini et al. investigated the effects of gamma irradiation on stored platelets, revealing a pro-apoptotic state that does not progress to overt apoptosis, indicating a complex interplay between radiation exposure and cellular responses (ref: Hosseini doi.org/10.1007/s10495-023-01841-5/). This finding suggests that radiation may induce subtle changes in cellular behavior that could influence treatment outcomes. In another study, Ju et al. identified TXNL4B as a regulator of radioresistance through its control of PRP3-mediated alternative splicing of FANCI, highlighting the role of splicing mechanisms in modulating cellular responses to radiation (ref: Ju doi.org/10.1002/mco2.258/). This underscores the potential for targeting splicing factors as a therapeutic strategy to overcome resistance. Furthermore, Spratt et al. evaluated genomic classifiers in intermediate-risk prostate cancer, demonstrating that lower genomic classifier scores correlate with significantly better metastasis-free survival, suggesting that genomic profiling can guide treatment decisions (ref: Spratt doi.org/10.1016/j.ijrobp.2023.04.010/). These studies collectively emphasize the importance of understanding cancer biology and resistance mechanisms to inform the development of more effective therapeutic strategies.

Clinical trials play a pivotal role in advancing cancer treatment and understanding patient outcomes. Recent findings from the STAMPEDE platform trials revealed that the combination of abiraterone acetate and enzalutamide significantly improves overall survival in patients with metastatic prostate cancer starting androgen deprivation therapy, with a median overall survival of 73.1 months compared to 51.8 months in the standard care group (ref: Attard doi.org/10.1016/S1470-2045(23)00148-1/). This highlights the importance of combination therapies in enhancing treatment efficacy. Additionally, Yu et al. investigated the association of circulating cardiomyocyte cell-free DNA with cancer therapy-related cardiac dysfunction in patients undergoing treatment for ERBB2-positive breast cancer, finding that elevated levels of cfDNA were linked to subsequent cardiac dysfunction (ref: Yu doi.org/10.1001/jamacardio.2023.1229/). This suggests that monitoring cfDNA could serve as a valuable biomarker for assessing treatment-related cardiac risks. Moreover, Kalashnikov et al. conducted a nationwide study on the risk of transformation and survival in marginal zone lymphoma, revealing that transformation significantly increases mortality risk, emphasizing the need for vigilant monitoring in this patient population (ref: Kalashnikov doi.org/10.1038/s41408-023-00831-9/). These findings collectively underscore the critical role of clinical trials in shaping treatment strategies and improving patient outcomes, as well as the necessity for ongoing evaluation of treatment-related risks.

The development of innovative photosensitizers is crucial for enhancing the efficacy of photodynamic therapy (PDT) in cancer treatment. Recent studies have focused on designing near-infrared (NIR)-triggered metallo-photosensitizers that can improve therapeutic outcomes by reducing vibrational relaxation processes, thereby increasing phototherapeutic efficacy (ref: Zhao doi.org/10.1021/jacs.3c01645/). This approach highlights the potential of molecular design in optimizing photosensitizers for clinical applications. Additionally, Wang et al. introduced self-immolative photosensitizers that can change fluorescence upon light illumination, enabling precise targeting and visualization of therapeutic processes, which is essential for personalized medicine (ref: Wang doi.org/10.1021/jacs.3c01666/). Furthermore, Ye et al. explored the use of mitochondria-targeting pyroptosis amplifiers for glioblastoma treatments, demonstrating that these agents can enhance immune activation by inducing pyroptosis, thus reprogramming the TME (ref: Ye doi.org/10.1021/acsami.3c01559/). This innovative strategy underscores the potential of combining immunogenic cell death with PDT to improve therapeutic outcomes. Lastly, Sun et al. proposed a "chase and block" strategy that synergizes hypoxia-promoted PDT with autophagy inhibition, offering a novel approach to amplify cancer therapy effects (ref: Sun doi.org/10.1002/adhm.202301087/). Collectively, these studies emphasize the ongoing advancements in photosensitizer design and the potential for enhancing PDT through innovative therapeutic strategies.

Epigenetic modifications play a significant role in tumor evolution and response to environmental factors, including radiation exposure. Bondarenko et al. conducted a comparative analysis of epigenetic variability in pine species exposed to chronic radiation in Chernobyl and Fukushima, revealing significant genetic variability and alterations in genome methylation and hydroxymethylation (ref: Bondarenko doi.org/10.1016/j.envpol.2023.121799/). This study highlights the impact of environmental stressors on epigenetic changes, which may inform our understanding of cancer susceptibility in affected populations. In the context of cancer therapy, Kath et al. explored the use of CAR NK-92 cells to deplete residual TCR+ cells in allogeneic CAR T-cell products, aiming to reduce the risk of graft-versus-host disease (GVHD) (ref: Kath doi.org/10.1182/bloodadvances.2022009397/). This approach underscores the importance of gene editing in improving the safety and efficacy of CAR T-cell therapies. Additionally, Vandenberg et al. investigated the contributions of DNA polymerases to mutagenic bypass of UV photoproducts, revealing insights into the mechanisms of mutation accumulation in skin cancers (ref: Vandenberg doi.org/10.1038/s41467-023-38255-5/). These findings collectively emphasize the critical role of epigenetics in tumor evolution and the potential for targeting epigenetic modifications in cancer therapy.

Patient-derived models are increasingly recognized as valuable tools for preclinical studies and treatment stratification in cancer research. Millen et al. demonstrated the utility of patient-derived head and neck cancer organoids for biomarker validation and treatment response prediction, indicating that organoid responses can closely mimic clinical outcomes (ref: Millen doi.org/10.1016/j.medj.2023.04.003/). This suggests that organoids can serve as a reliable platform for evaluating therapeutic strategies and personalizing treatment approaches. Moreover, Mann et al. developed an organotypic brain slice culture-based platform that enables rapid engraftment and analysis of patient tumor tissue, supporting the notion that patient-derived models can facilitate functional precision medicine (ref: Mann doi.org/10.1016/j.xcrm.2023.101042/). This platform allows for the maintenance of the tumor's original DNA profile, providing insights into tumor biology and treatment responses. Additionally, Bui et al. evaluated circulating tumor DNA (ctDNA) as a biomarker for monitoring response to immunotherapy combined with local cryotherapy in soft tissue sarcomas, highlighting the potential of ctDNA in assessing treatment efficacy (ref: Bui doi.org/10.1158/1078-0432.CCR-23-0250/). Collectively, these studies underscore the importance of patient-derived models in advancing cancer research and improving treatment outcomes.