Recent advancements in the analysis of circulating tumor DNA (ctDNA) have significantly enhanced cancer detection methodologies. Helzer et al. employed machine learning models to analyze fragmentation patterns in ctDNA from targeted cancer gene sequencing panels, achieving an impressive accuracy of 86.6% in distinguishing cancer patients from non-cancer patients in an independent validation cohort, despite a low median ctDNA fraction of 0.06 (ref: Helzer doi.org/10.1016/j.annonc.2023.06.001/). In a large-scale observational study by Nicholson et al., a methylation-based multi-cancer early detection test demonstrated a sensitivity of 66.7% and a specificity of 98.4% in symptomatic patients, with an 85.2% accuracy in predicting the site of cancer origin (ref: Nicholson doi.org/10.1016/S1470-2045(23)00277-2/). Furthermore, Fan et al. developed novel prediction models for hepatocellular carcinoma (HCC) using longitudinal data and ctDNA signatures, which could guide individualized surveillance strategies (ref: Fan doi.org/10.1016/j.jhep.2023.05.039/). These studies collectively underscore the potential of ctDNA as a non-invasive biomarker for early cancer detection and monitoring, with implications for personalized treatment approaches. In the context of specific cancers, Jung et al. highlighted the utility of longitudinal ctDNA monitoring in patients with EGFR-mutant non-small cell lung cancer (NSCLC), where minimal residual disease (MRD) was detected in 69% of patients prior to radiological recurrence (ref: Jung doi.org/10.1016/j.jtho.2023.05.027/). Similarly, Gray et al. found that early clearance of plasma EGFR mutations correlated with improved progression-free survival in advanced NSCLC patients treated with osimertinib (ref: Gray doi.org/10.1158/1078-0432.CCR-22-3146/). The systematic review by Crupi et al. further confirmed the prognostic value of ctDNA in muscle-invasive bladder cancer, suggesting its role in selecting candidates for neoadjuvant therapies (ref: Crupi doi.org/10.1016/j.euo.2023.05.012/). Overall, these findings illustrate the critical role of ctDNA in enhancing cancer detection, prognostication, and treatment personalization across various malignancies.

The interplay between the immune response and the tumor microenvironment (TME) is crucial for understanding cancer progression and treatment efficacy. Lv et al. investigated the immune landscape of nasopharyngeal carcinoma (NPC) post-gemcitabine plus cisplatin treatment, revealing an innate-like B cell-dominant antitumor immune response activated by chemotherapy (ref: Lv doi.org/10.1038/s41591-023-02369-6/). This study emphasizes the need to explore how chemotherapy can reshape the TME to enhance immune responses. In a different context, Ratovomanana et al. focused on mismatch repair-deficient metastatic colorectal cancer, identifying resistance mechanisms to immune checkpoint inhibitors (ICIs) and the necessity for predictive tools to improve therapeutic outcomes (ref: Ratovomanana doi.org/10.1016/j.annonc.2023.05.010/). These findings highlight the importance of understanding the TME's role in mediating responses to immunotherapy. Moreover, Han et al. explored the changes in the TME following osimertinib treatment resistance in NSCLC, revealing a complex interaction between tumor cells and their microenvironment that contributes to therapeutic failure (ref: Han doi.org/10.1016/j.ejca.2023.05.007/). The study underscores the dynamic nature of the TME and its influence on treatment resistance. Additionally, innovative therapeutic strategies are being developed to target the TME, such as the macrophage-hitchhiked nanoparticles designed by Chen et al. for pancreatic cancer therapy, which aim to enhance drug delivery and efficacy (ref: Chen doi.org/10.1002/adma.202304735/). Collectively, these studies illustrate the critical role of the immune response and TME in cancer therapy, emphasizing the need for integrated approaches that consider these factors in treatment design.

Liquid biopsy technologies are revolutionizing cancer diagnostics and monitoring by enabling non-invasive analysis of tumor-derived materials. Haddock et al. developed a computational pipeline to identify bacteriophages in cell-free DNA from plasma samples, which could serve as a novel approach for detecting bacterial pathogens in sepsis cases (ref: Haddock doi.org/10.1038/s41564-023-01406-x/). This innovative methodology highlights the potential of liquid biopsies beyond traditional cancer markers, expanding their application in infectious diseases. In hepatocellular carcinoma (HCC), Wong et al. demonstrated that small extracellular vesicle-derived von Willebrand factor (vWF) levels correlate with disease progression, suggesting a role for these vesicles in tumor angiogenesis and metastasis (ref: Wong doi.org/10.1002/advs.202302677/). Furthermore, Cheishvili et al. introduced a high-throughput DNA methylation signature for HCC detection, validated against normal tissue profiles, showcasing the potential for early cancer detection through liquid biopsies (ref: Cheishvili doi.org/10.1038/s41467-023-39055-7/). Iwanaga et al. advanced the field with metasurface biosensors capable of single-molecule detection of cell-free DNA, achieving high statistical confidence in their results (ref: Iwanaga doi.org/10.1021/acs.nanolett.3c01527/). These studies collectively emphasize the rapid evolution of liquid biopsy technologies, which are becoming indispensable tools for cancer detection, monitoring, and potentially guiding therapeutic decisions.

Genomic profiling is increasingly recognized as a cornerstone for personalized cancer treatment, enabling the identification of actionable mutations and biomarkers. Li et al. conducted a comprehensive study on vascular anomalies, utilizing ultra-deep sequencing of cell-free DNA to uncover pathogenic variants in a cohort of 356 participants, including those with complex lymphatic anomalies (ref: Li doi.org/10.1038/s41591-023-02364-x/). This approach highlights the potential of genomic profiling in diagnosing and guiding treatment for rare vascular conditions. Additionally, Elias et al. developed a serum microRNA-based diagnostic test for identifying BRCA1/2 mutation carriers, which is crucial for breast and ovarian cancer risk reduction (ref: Elias doi.org/10.1038/s41467-023-38925-4/). Moreover, the study by Soo et al. on circulating tumor DNA dynamics in patients with advanced ALK-positive NSCLC revealed that molecular responses to lorlatinib were associated with improved progression-free survival, underscoring the importance of ctDNA as a biomarker for treatment efficacy (ref: Soo doi.org/10.1016/j.jtho.2023.05.021/). Jalali et al. explored the use of surface-enhanced Raman spectroscopy for real-time monitoring of tumor-derived extracellular vesicles, which could provide insights into glioblastoma progression (ref: Jalali doi.org/10.1021/acsnano.2c09222/). Collectively, these studies illustrate the transformative impact of genomic profiling and biomarker identification in enhancing cancer diagnosis, treatment personalization, and monitoring.

Understanding the mechanisms of cancer treatment resistance is critical for improving therapeutic outcomes. Facchinetti et al. investigated resistance to selective FGFR inhibitors in FGFR-driven urothelial cancer, identifying mutations in the FGFR tyrosine kinase domain in a subset of patients post-progression (ref: Facchinetti doi.org/10.1158/2159-8290.CD-22-1441/). This study highlights the need for ongoing genomic monitoring to adapt treatment strategies in real-time. Similarly, Haratani et al. conducted a multicenter prospective biomarker study to explore resistance mechanisms to PD-L1 blockade in NSCLC after chemoradiotherapy, revealing insights into the TME's role in mediating resistance (ref: Haratani doi.org/10.1016/j.jtho.2023.06.012/). In the context of melanoma, Randic et al. utilized single-cell transcriptomics to identify early drug response indicators in NRAS-mutated melanoma transitioning to drug resistance, emphasizing the importance of understanding cellular adaptations in response to therapy (ref: Randic doi.org/10.1016/j.celrep.2023.112696/). Furthermore, Han et al. explored the remodeling of the TME following osimertinib treatment resistance in NSCLC, suggesting that the interaction between tumor cells and their microenvironment contributes significantly to therapeutic failure (ref: Han doi.org/10.1016/j.ejca.2023.05.007/). These findings collectively underscore the complexity of treatment resistance mechanisms and the necessity for innovative strategies to overcome them in various cancer types.

Early detection and monitoring of cancer are pivotal for improving patient outcomes, and recent studies have highlighted innovative approaches in this area. Wong et al. demonstrated that small extracellular vesicle-derived von Willebrand factor (vWF) levels are progressively upregulated in hepatocellular carcinoma (HCC), suggesting a potential biomarker for early detection and monitoring of disease progression (ref: Wong doi.org/10.1002/advs.202302677/). This finding aligns with Cheishvili et al.'s work on a high-throughput DNA methylation signature for HCC detection, which could revolutionize early cancer diagnostics by distinguishing cancerous from normal tissues (ref: Cheishvili doi.org/10.1038/s41467-023-39055-7/). Additionally, Zhao et al. introduced carrier-free nanoproteolysis targeting chimeras (PROTACs) designed to enhance photodynamic therapy (PDT) by amplifying DNA damage through BRD4 degradation, showcasing a novel strategy for improving therapeutic efficacy (ref: Zhao doi.org/10.1021/acs.nanolett.3c01812/). These advancements in early detection and monitoring underscore the importance of integrating innovative technologies and methodologies to enhance cancer management strategies, ultimately leading to better patient outcomes.

The relationship between the microbiome and cancer is an emerging area of research that reveals significant insights into cancer development and progression. Kang et al. investigated the role of obesity-associated gut microbiota in promoting colorectal carcinogenesis, demonstrating that altered microbiota can enhance cancer risk in a mouse model (ref: Kang doi.org/10.1016/j.ebiom.2023.104670/). This study provides compelling evidence for the microbiome's influence on cancer risk and highlights potential therapeutic targets for intervention. In addition, the findings from Cheishvili et al. on the DNA methylation signature for hepatocellular carcinoma detection further emphasize the potential of integrating microbiome analysis with liquid biopsy technologies for early cancer detection (ref: Cheishvili doi.org/10.1038/s41467-023-39055-7/). The interplay between the microbiome and cancer therapies is also critical, as the microbiome can modulate the efficacy of immunotherapies and other treatments. This growing body of evidence suggests that understanding the microbiome's role in cancer could lead to novel strategies for prevention, diagnosis, and treatment, ultimately improving patient outcomes.

Innovative therapeutic strategies are crucial for advancing cancer treatment and improving patient outcomes. Ye et al. introduced a rapid method for generating CD19 CAR-T cells using minicircle DNA, significantly reducing the time required for cell manufacturing while maintaining therapeutic efficacy (ref: Ye doi.org/10.1016/j.canlet.2023.216278/). This advancement could enhance the accessibility and feasibility of CAR-T cell therapies for leukemia patients. Additionally, Zhao et al. developed carrier-free nanoproteolysis targeting chimeras (PROTACs) to amplify photodynamic therapy-induced DNA damage, showcasing a novel approach to enhance the effectiveness of existing therapies (ref: Zhao doi.org/10.1021/acs.nanolett.3c01812/). Moreover, Wong et al. highlighted the role of small extracellular vesicle-derived von Willebrand factor (vWF) in promoting angiogenesis and metastasis in hepatocellular carcinoma, suggesting that targeting these vesicles could represent a new therapeutic avenue (ref: Wong doi.org/10.1002/advs.202302677/). Collectively, these studies illustrate the dynamic landscape of therapeutic innovations in cancer treatment, emphasizing the need for continued exploration of novel strategies to enhance efficacy and patient outcomes.