Circulating tumor DNA (ctDNA) has emerged as a pivotal biomarker in cancer management, particularly for tailoring therapies in advanced solid tumors. A prospective study demonstrated that comprehensive molecular profiling of ctDNA can effectively match patients with targeted therapies, highlighting its clinical utility (ref: Bayle doi.org/10.1016/j.annonc.2023.01.008/). In gastrointestinal cancers, ctDNA is increasingly integrated into clinical practice, although its impact on upper gastrointestinal tumors remains limited (ref: Pretta doi.org/10.5306/wjco.v13.i12.980/). Furthermore, the use of exosomal miRNAs as biomarkers for lymph node metastasis in T1 colorectal cancer showed promising results, with a specific panel of miRNAs demonstrating robust predictive capabilities (ref: Miyazaki doi.org/10.1186/s12943-022-01685-8/). The association of postsurgical ctDNA positivity with recurrence risk in colorectal cancer underscores its prognostic significance, with a hazard ratio of 10.0 indicating a substantial risk of relapse (ref: Kotani doi.org/10.1038/s41591-022-02115-4/). Additionally, the analysis of cerebrospinal fluid for glioma molecular profiling presents a novel approach for cases where tumor tissue is inaccessible (ref: Orzan doi.org/10.1158/1078-0432.CCR-22-2903/). Methylation markers in ctDNA have also been identified as promising tools for monitoring treatment responses in metastatic colorectal cancer (ref: Janssens doi.org/10.1158/1078-0432.CCR-22-1500/). Overall, these studies collectively emphasize the evolving role of liquid biopsies in enhancing diagnostic accuracy and treatment personalization in oncology.

Tumor mutational burden (TMB) has been scrutinized for its potential as a biomarker in cancer treatment, particularly in the context of immunotherapy. A retrospective analysis from the KEYNOTE-042 trial evaluated the clinical utility of tissue TMB and specific mutations in patients with advanced PD-L1-positive non-small-cell lung cancer (NSCLC). The study found that TMB could serve as a predictive marker for treatment outcomes, particularly when assessed against a predefined threshold (ref: Mok doi.org/10.1016/j.annonc.2023.01.011/). In a broader pan-cancer analysis, persistent mutation burden was shown to drive sustained anti-tumor immune responses, suggesting that TMB may impose an evolutionary bottleneck that enhances immunologic control (ref: Niknafs doi.org/10.1038/s41591-022-02163-w/). Contrastingly, the genetic landscape of Richter syndrome, which arises from chronic lymphocytic leukemia, revealed specific somatic mutations and copy-number alterations that could inform treatment strategies (ref: Parry doi.org/10.1038/s41591-022-02113-6/). The integration of TMB with other biomarkers, such as STING stimulation in dendritic cells, may further refine therapeutic approaches by priming antitumor T cell responses (ref: Jneid doi.org/10.1126/sciimmunol.abn6612/). Collectively, these findings underscore the complexity of TMB as a biomarker and its implications for personalized cancer therapy.

Immunotherapy has revolutionized cancer treatment, with various studies exploring the modulation of immune responses to enhance therapeutic efficacy. A phase I study of anti-PD-1 therapy demonstrated safety and preliminary antitumor activity in patients with refractory solid tumors, indicating the potential of PD-1 blockade in diverse malignancies (ref: Brahmer doi.org/10.1200/JCO.22.02270/). Additionally, the EVICT trial investigated the combination of BRAF and EGFR inhibitors in BRAF V600E positive metastatic colorectal cancer, revealing a safe and effective treatment strategy that highlights the importance of targeted therapies in immunotherapy (ref: Tan doi.org/10.1158/1078-0432.CCR-22-3094/). The role of circulating tumor DNA (ctDNA) in predicting immunotherapy efficacy was also examined, with short-term dynamics post-treatment serving as a robust biomarker for therapeutic response (ref: Han doi.org/10.1136/jitc-2022-004952/). Furthermore, the activation of MAIT cells in NSCLC patients correlated with anti-PD-1 immunotherapy outcomes, suggesting that immune cell profiling could guide treatment decisions (ref: Shi doi.org/10.1136/jitc-2022-005902/). These studies collectively illustrate the intricate interplay between immunotherapy and immune modulation, emphasizing the need for personalized approaches in cancer treatment.

The exploration of molecular mechanisms and genetic profiling in cancer has provided significant insights into tumor biology and treatment resistance. A study utilizing an evolved AAV variant demonstrated efficient genetic engineering of murine T cells, which could enhance adoptive cell therapies and advance T cell immunology (ref: Nyberg doi.org/10.1016/j.cell.2022.12.022/). Additionally, research on mRNA localization elements in primary cortical neurons has implications for understanding gene expression regulation in cancer (ref: Mendonsa doi.org/10.1038/s41593-022-01243-x/). The identification of exosomal microRNAs as biomarkers for cancer monitoring was achieved through a novel target recycling amplification process, showcasing the potential for early detection and treatment response assessment (ref: Wang doi.org/10.1002/anie.202217932/). Furthermore, a genome-wide association study on chemotherapy-related hyperbilirubinemia in pediatric acute lymphoblastic leukemia highlighted the importance of genetic factors in treatment outcomes (ref: Junk doi.org/10.1186/s13046-022-02585-x/). These findings underscore the critical role of genetic profiling in elucidating cancer mechanisms and informing therapeutic strategies.

Extracellular vesicles (EVs) and exosomes are increasingly recognized for their roles in cancer biology and potential as therapeutic targets. A study demonstrated that nanoparticulate cationic poly(amino acid)s can block cancer metastases by disrupting neutrophil extracellular traps, indicating a novel approach to inhibit tumor spread (ref: Liang doi.org/10.1021/acsnano.2c11280/). Additionally, the development of a prostate cancer extracellular vesicle digital scoring assay allows for noninvasive quantification of disease-relevant mRNAs, enhancing disease monitoring and treatment response evaluation (ref: Wang doi.org/10.1016/j.nantod.2022.101746/). The dynamics of circulating galectin-1 were shown to delineate responses to bevacizumab in melanoma patients, further illustrating the role of EVs in modulating tumor microenvironments and therapeutic responses (ref: Bannoud doi.org/10.1073/pnas.2214350120/). Moreover, the integration of micro-combinatorial hydrogel particles for targeted chemotherapy delivery in advanced breast cancer lung metastasis highlights innovative strategies to enhance therapeutic efficacy (ref: Palange doi.org/10.1002/advs.202205223/). Collectively, these studies emphasize the potential of EVs and exosomes as biomarkers and therapeutic targets in cancer treatment.

Liquid biopsy technologies have transformed cancer diagnostics and monitoring by providing minimally invasive methods to assess tumor dynamics. A study on circulating tumor DNA (ctDNA) dynamics demonstrated its predictive value for immunotherapy efficacy in advanced non-small cell lung cancer, underscoring the importance of real-time monitoring of tumor responses (ref: Han doi.org/10.1136/jitc-2022-004952/). Additionally, the application of nanoparticulate cationic materials to block cancer metastases by targeting neutrophil extracellular traps illustrates innovative methodologies for enhancing therapeutic outcomes (ref: Liang doi.org/10.1021/acsnano.2c11280/). The development of a digital scoring assay for prostate cancer extracellular vesicles enables rapid and precise quantification of disease-relevant mRNAs, facilitating noninvasive monitoring of disease progression (ref: Wang doi.org/10.1016/j.nantod.2022.101746/). Furthermore, the identification of CD83 expression on GVHD effector cells in hematopoietic cell transplantation highlights the potential of liquid biopsies in predicting clinical outcomes and guiding therapeutic interventions (ref: Holtan doi.org/10.1158/1078-0432.CCR-22-2837/). These advancements collectively emphasize the critical role of liquid biopsy technologies in enhancing cancer management and patient care.

Clinical trials continue to play a vital role in advancing cancer treatment and understanding treatment outcomes. A phase 1b-2 study evaluating the combination of the CD73 inhibitor oleclumab with osimertinib in advanced EGFR-mutated non-small cell lung cancer demonstrated promising response rates, with a median overall survival of 24.8 months in specific patient cohorts (ref: Kim doi.org/10.1016/j.jtho.2022.12.021/). The analysis of molecular residual disease in colorectal cancer revealed that postsurgical ctDNA positivity significantly correlates with recurrence risk, providing critical insights for adjuvant chemotherapy decisions (ref: Kotani doi.org/10.1038/s41591-022-02115-4/). Additionally, the genome-wide analysis of plasma DNA fragment ends has opened avenues for novel cancer diagnostics by revealing tumor-derived DNA presence in blood (ref: Budhraja doi.org/10.1126/scitranslmed.abm6863/). The integration of these findings into clinical practice emphasizes the importance of molecular profiling and ctDNA monitoring in improving patient outcomes and personalizing treatment strategies.