Circulating tumor DNA (ctDNA) has emerged as a pivotal biomarker in cancer diagnostics and monitoring, particularly in the context of liquid biopsies. A systematic review and meta-analysis by Valenza et al. demonstrated that ctDNA clearance can predict pathologic complete response (pCR) in patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitors (ICIs), reporting a pooled sensitivity of 0.98 and a specificity of 0.53 (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). This finding underscores the potential of ctDNA as a non-invasive biomarker for treatment efficacy. Furthermore, Andrews et al. provided evidence that ctDNA clearance within 10 weeks of initiating tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC) correlates with improved overall survival (OS) and progression-free survival (PFS), highlighting the clinical utility of ctDNA in monitoring therapeutic responses (ref: Andrews doi.org/10.1158/1078-0432.CCR-24-3612/). In a different context, Bercz et al. found that the presence of circulating tumor HPV DNA post-chemoradiation in anal cancer patients is associated with disease recurrence, suggesting that ctDNA can serve as a prognostic marker for early intervention (ref: Bercz doi.org/10.1158/1078-0432.CCR-25-0421/). Collectively, these studies illustrate the diverse applications of ctDNA in predicting treatment outcomes and monitoring disease progression across various cancer types, reinforcing its role in personalized medicine.

The interplay between the immune system and cancer therapies is a critical area of research, particularly regarding immune checkpoint inhibitors (ICIs). Cercek et al. demonstrated that nonoperative management following neoadjuvant PD-1 blockade in mismatch repair-deficient tumors resulted in a clinical complete response in a significant proportion of patients, suggesting that organ preservation strategies can be effective in early-stage cancers (ref: Cercek doi.org/10.1056/NEJMoa2404512/). In contrast, Cheng et al. revealed that bone metastases can diminish the efficacy of ICIs in extraosseous tumors, mediated by osteopontin-producing osteoclasts, which may complicate treatment strategies for patients with metastatic disease (ref: Cheng doi.org/10.1016/j.ccell.2025.03.036/). Additionally, the study by Kao et al. highlighted age-related differences in immune responses to ICIs, indicating that older patients may exhibit altered immune profiles that could affect treatment outcomes (ref: Kao doi.org/10.1038/s41467-025-58512-z/). These findings emphasize the necessity of tailoring immunotherapy approaches based on individual patient characteristics, including tumor genetics and patient age, to optimize therapeutic efficacy.

Genomic profiling has revolutionized cancer treatment by enabling personalized therapy based on tumor characteristics. The Copenhagen Prospective Personalized Oncology (CoPPO) study reported significant impacts of comprehensive genomic profiling in over 2000 patients, demonstrating the utility of targeted therapies based on molecular tumor characterization (ref: Belcaid doi.org/10.1016/j.annonc.2025.04.004/). In melanoma management, Syeda et al. validated droplet digital PCR assays for detecting BRAF mutations in ctDNA, establishing its potential to predict survival outcomes and identify patients at high risk of recurrence during adjuvant therapy (ref: Syeda doi.org/10.1016/S1470-2045(25)00139-1/). Furthermore, Liu et al. introduced DirectHRD, a novel method for detecting homologous recombination deficiency (HRD) through genomic scars, which is crucial for identifying patients who may benefit from PARP inhibitors (ref: Liu doi.org/10.1093/nar/). These studies collectively highlight the importance of genomic profiling in enhancing treatment precision and improving patient outcomes in various cancer types.

Addressing drug resistance in cancer therapy remains a significant challenge. Hockings et al. explored adaptive therapy as a strategy to exploit fitness deficits in chemotherapy-resistant ovarian cancer, demonstrating that adjusting carboplatin doses based on tumor response significantly prolonged survival without increasing toxicity (ref: Hockings doi.org/10.1158/0008-5472.CAN-25-0351/). In a different approach, Jang et al. investigated the combination of Ad-SGE-DKK3 gene therapy with nivolumab in pleural mesothelioma, reporting a 16.6% objective response rate and a 58.3% rate of durable clinical response, indicating potential efficacy in overcoming resistance to ICIs (ref: Jang doi.org/10.1158/1078-0432.CCR-24-4024/). Additionally, Wang et al. highlighted the role of the mRNA export pathway in enhancing antitumor immunity by facilitating the export of nuclear retroelement transcripts, which can trigger immune responses (ref: Wang doi.org/10.1126/scitranslmed.ado4370/). These findings underscore the necessity for innovative therapeutic strategies to combat resistance and improve treatment outcomes in cancer patients.

The cancer microenvironment and metabolic pathways play crucial roles in tumor progression and response to therapy. Zhang et al. developed a dynamically regulating hydrogel that promotes rapid wound healing while suppressing scar formation, showcasing the potential of biomaterials in regenerative medicine (ref: Zhang doi.org/10.1038/s41467-025-58987-w/). In another study, Bohm et al. demonstrated that the gut microbiome enhances breast cancer immunotherapy outcomes following bariatric surgery, suggesting that microbial composition may influence therapeutic efficacy (ref: Bohm doi.org/10.1172/jci.insight.187683/). These studies highlight the intricate relationship between cancer metabolism, the tumor microenvironment, and therapeutic responses, emphasizing the need for integrated approaches that consider both biological and environmental factors in cancer treatment.

Recent advancements in liquid biopsy technologies have significantly enhanced the detection and monitoring of cancer. Cheng et al. introduced error-corrected flow-based sequencing at a whole-genome scale, addressing the challenges of sequencing errors in circulating cell-free DNA (ccfDNA) profiling, which is crucial for cancer monitoring (ref: Cheng doi.org/10.1038/s41592-025-02648-9/). Additionally, the CoPPO study highlighted the impact of comprehensive genomic profiling in over 2000 patients, demonstrating the effectiveness of targeted therapies based on molecular characterization (ref: Belcaid doi.org/10.1016/j.annonc.2025.04.004/). Syeda et al. further validated droplet digital PCR assays for detecting BRAF mutations in ctDNA, reinforcing the role of liquid biopsies in predicting patient outcomes (ref: Syeda doi.org/10.1016/S1470-2045(25)00139-1/). These technological innovations underscore the transformative potential of liquid biopsies in cancer diagnostics and personalized treatment strategies.

Clinical trials play a pivotal role in determining the efficacy of new cancer therapies and understanding patient outcomes. Cercek et al. reported that nonoperative management following neoadjuvant PD-1 blockade in mismatch repair-deficient tumors resulted in a high rate of clinical complete responses, suggesting a promising approach for organ preservation (ref: Cercek doi.org/10.1056/NEJMoa2404512/). In contrast, Honoré et al. utilized a personalized tumor-informed ctDNA assay to predict recurrence in locally advanced squamous-cell carcinoma of the head and neck, finding that ctDNA positivity post-treatment was predictive of worse recurrence-free survival (RFS) and overall survival (OS) (ref: Honoré doi.org/10.1016/j.esmoop.2025.104534/). Additionally, the study by Wang et al. on robot-assisted tumor thrombectomy demonstrated the feasibility and reproducibility of this surgical technique, contributing to improved patient outcomes in complex cases (ref: Wang doi.org/10.1016/j.eururo.2025.04.001/). These findings highlight the importance of clinical trials in shaping treatment paradigms and enhancing patient care in oncology.