The exploration of circulating tumor DNA (ctDNA) as a biomarker for cancer prognosis has gained significant traction, particularly in metastatic colorectal cancer (mCRC). A pivotal study from the PARADIGM trial demonstrated that specific ctDNA gene alterations, such as those in KRAS and NRAS, correlate with resistance to anti-EGFR therapies, highlighting the potential of ctDNA to guide treatment decisions (ref: Shitara doi.org/10.1038/s41591-023-02791-w/). Additionally, early changes in ctDNA levels have been shown to predict outcomes in patients treated with pembrolizumab across various solid tumors, indicating that ctDNA kinetics can serve as a reliable prognostic tool independent of tumor type and PD-L1 expression (ref: Stutheit-Zhao doi.org/10.1158/2159-8290.CD-23-1060/). In prostate cancer, a comprehensive analysis of ctDNA fraction across multiple trials revealed its potential utility in risk stratification, although consensus on its clinical application remains elusive (ref: Fonseca doi.org/10.1038/s41467-024-45475-w/). Furthermore, the detection of ctDNA prior to surgery in lung cancer patients was significantly associated with shorter recurrence-free survival, underscoring its role in monitoring minimal residual disease (ref: Tan doi.org/10.1002/cncr.35263/). The genomic landscape of liquid biopsies has also been characterized, with a substantial proportion of mutations found in TP53 and DNA damage response genes, suggesting that ctDNA analysis can provide insights into tumor biology and treatment resistance (ref: Vasseur doi.org/10.1038/s41698-024-00544-7/). Lastly, the identification of microRNA biomarkers, such as MIR652-3p, has been linked to resistance mechanisms in colorectal cancer, further emphasizing the multifaceted role of ctDNA and associated biomarkers in cancer management (ref: Hedayat doi.org/10.1158/1078-0432.CCR-23-2748/).

Liquid biopsy technologies are revolutionizing cancer diagnostics and monitoring through non-invasive methods. A multicancer screening test developed to detect circulating atypical cells aims to address the challenge of early cancer diagnosis by identifying individuals at risk before clinical symptoms manifest (ref: Malara doi.org/10.1186/s12943-024-01951-x/). The application of serum amyloid A as a biomarker for predicting resistance to PD-1 blockade in hepatocellular carcinoma has shown promise, with elevated levels correlating with treatment failure, thus providing a potential target for therapeutic intervention (ref: He doi.org/10.1038/s41467-024-46118-w/). Furthermore, the use of ultradeep sequencing of plasma cell-free DNA has demonstrated efficacy in monitoring minimal residual disease and early recurrence in lung cancer, with presurgical ctDNA detection significantly associated with poorer outcomes (ref: Tan doi.org/10.1002/cncr.35263/). Advances in single-cell sequencing technologies have enabled accurate detection of circulating tumor cells (CTCs), enhancing the potential for liquid biopsy applications in multi-cancer diagnosis (ref: Shen doi.org/10.1038/s41698-024-00520-1/). Additionally, innovative methods such as a quantum dot-based aptasensor guided by CRISPR/Cas12a have been developed for direct measurement of CTCs, showcasing the integration of nanotechnology in liquid biopsy approaches (ref: Zhang doi.org/10.1021/acs.nanolett.3c04828/). These advancements highlight the evolving landscape of liquid biopsy technologies, which are increasingly recognized for their role in cancer screening, monitoring, and personalized treatment strategies.

Understanding the mechanisms of resistance to cancer immunotherapy is crucial for improving treatment outcomes. A phase 2 umbrella trial investigating biomarker-directed therapy combined with durvalumab in advanced non-small-cell lung cancer (NSCLC) revealed that not all patients benefit from anti-PD-(L)1 therapies, with resistance often linked to defects in DNA damage response pathways and alterations in antigen-presentation mechanisms (ref: Besse doi.org/10.1038/s41591-024-02808-y/). Myeloid-derived suppressor cells (MDSCs) have emerged as significant players in tumor immunoevasion, with FFAR2 expression in these cells correlating with poor prognosis in lung adenocarcinoma, suggesting that targeting MDSCs may enhance immunotherapy efficacy (ref: Zhao doi.org/10.1186/s13045-024-01529-6/). Additionally, serum amyloid A has been implicated in promoting glycolysis in neutrophils during PD-1 blockade resistance in hepatocellular carcinoma, indicating a potential biomarker for predicting treatment failure (ref: He doi.org/10.1038/s41467-024-46118-w/). The OSCILLATE trial explored alternating osimertinib and gefitinib in EGFR-T790M positive NSCLC, aiming to delay resistance development; however, the primary endpoint of progression-free survival was not met, highlighting the challenges in overcoming resistance (ref: Tan doi.org/10.1038/s41467-024-46008-1/). Furthermore, a study on T-cell-to-stroma enrichment scores identified predictive markers for response to immune checkpoint inhibitors in urothelial cancer, emphasizing the need for personalized approaches in immunotherapy (ref: Rijnders doi.org/10.1038/s41467-024-45714-0/).

Exosomes and extracellular vesicles (EVs) play a critical role in cancer progression and metastasis. Research has shown that tumor-derived exosomal ADAM17 enhances vascular permeability, facilitating pre-metastatic niche formation in colorectal cancer, which underscores the importance of exosomal components in the metastatic process (ref: Li doi.org/10.1186/s13046-024-02991-3/). Additionally, the infiltration of granulocytic myeloid-derived suppressor cells (gMDSCs) into the lung premetastatic niche has been linked to osteosarcoma, indicating that exosome-mediated communication between tumor cells and the microenvironment is pivotal for metastasis (ref: Deng doi.org/10.1016/j.celrep.2024.113751/). The interplay between exosomes and immune cells, particularly MDSCs, highlights the potential for targeting these pathways to improve cancer immunotherapy outcomes (ref: Zhao doi.org/10.1186/s13045-024-01529-6/). Furthermore, the development of novel technologies for CTC detection, such as a quantum dot-based aptasensor, illustrates the innovative approaches being employed to harness the potential of exosomes and EVs in cancer diagnostics and monitoring (ref: Zhang doi.org/10.1021/acs.nanolett.3c04828/). These findings collectively emphasize the significance of exosomes and EVs in cancer biology, particularly in the context of metastasis and therapeutic resistance.

Genomic and transcriptomic profiling is increasingly recognized for its potential to inform cancer diagnosis and treatment. A comprehensive study on autoantibody profiling in advanced urothelial cancer identified specific autoantibodies associated with response and resistance to immune checkpoint inhibitors, providing insights into potential biomarkers for therapeutic efficacy (ref: Ravi doi.org/10.1136/jitc-2023-008215/). Additionally, the transcriptomic signature of exosomes enriched from hepatocellular carcinoma has been explored as a novel approach for early detection and monitoring of disease progression, highlighting the utility of exosomal biomarkers in clinical settings (ref: Yi doi.org/10.1002/advs.202305204/). The investigation into the fraction of cellular DNA turnover that becomes cell-free DNA (cfDNA) has provided valuable insights into the dynamics of cfDNA in the bloodstream, which can serve as a non-invasive biomarker for cancer (ref: Sender doi.org/10.7554/eLife.89321/). Furthermore, aging-related changes in nucleosome organization have been linked to gene expression alterations, suggesting that cfDNA analysis could also provide insights into biological aging and its implications for cancer (ref: Shtumpf doi.org/10.1111/acel.14100/). The development of single-cell low-pass whole genome sequencing for CTC detection represents a significant advancement in liquid biopsy technologies, enabling more accurate cancer diagnosis and monitoring (ref: Shen doi.org/10.1038/s41698-024-00520-1/). These studies collectively underscore the importance of genomic and transcriptomic profiling in enhancing our understanding of cancer biology and improving patient outcomes.

The field of cancer screening and early detection is rapidly evolving, with innovative approaches aimed at identifying malignancies at earlier stages. A multicancer screening test that detects circulating non-haematological proliferating atypical cells has been developed to address the challenge of early cancer diagnosis, focusing on predictive models that can identify individuals at risk before clinical symptoms arise (ref: Malara doi.org/10.1186/s12943-024-01951-x/). In hepatocellular carcinoma, serum amyloid A has been identified as a potential biomarker for predicting resistance to PD-1 blockade, with elevated levels correlating with treatment failure, thus providing a novel avenue for early detection and monitoring (ref: He doi.org/10.1038/s41467-024-46118-w/). The detection of ctDNA prior to surgery in lung cancer patients has been significantly associated with shorter recurrence-free survival, emphasizing its role in monitoring minimal residual disease and early recurrence (ref: Tan doi.org/10.1002/cncr.35263/). In prostate cancer, the prognostic implications of ctDNA fraction have been explored, revealing its potential utility in risk stratification, although consensus on its clinical application remains to be established (ref: Fonseca doi.org/10.1038/s41467-024-45475-w/). Additionally, a novel saliva-based microRNA profile has been developed for diagnosing and predicting oral cancer, showcasing the potential of non-invasive biomarkers in early detection strategies (ref: Balakittnen doi.org/10.1038/s41368-023-00273-w/). These advancements highlight the critical importance of early detection and screening in improving cancer outcomes and patient survival.

Therapeutic monitoring and treatment response assessment are crucial components of cancer management, particularly in the context of liquid biopsies. A study examining the prognostic implications of ctDNA fraction in metastatic castration-resistant prostate cancer (mCRPC) revealed its potential utility in risk stratification, although consensus on its clinical application remains unclear (ref: Fonseca doi.org/10.1038/s41467-024-45475-w/). The detection of ctDNA prior to surgery in lung cancer patients was significantly associated with shorter recurrence-free survival, underscoring its role in monitoring minimal residual disease and early detection of recurrence (ref: Tan doi.org/10.1002/cncr.35263/). Additionally, serum amyloid A has been implicated in promoting glycolysis in neutrophils during PD-1 blockade resistance in hepatocellular carcinoma, indicating its potential as a biomarker for predicting treatment failure (ref: He doi.org/10.1038/s41467-024-46118-w/). The OSCILLATE trial explored alternating osimertinib and gefitinib in EGFR-T790M positive NSCLC, aiming to delay resistance development; however, the primary endpoint of progression-free survival was not met, highlighting the challenges in overcoming resistance (ref: Tan doi.org/10.1038/s41467-024-46008-1/). Furthermore, the development of single-cell low-pass whole genome sequencing for CTC detection represents a significant advancement in liquid biopsy technologies, enabling more accurate cancer diagnosis and monitoring (ref: Shen doi.org/10.1038/s41698-024-00520-1/). These findings collectively emphasize the importance of therapeutic monitoring and treatment response assessment in optimizing cancer management strategies.

Cancer metastasis and the tumor microenvironment are critical areas of research that influence treatment outcomes. A study on tumor-derived exosomal ADAM17 highlighted its role in enhancing vascular permeability and promoting pre-metastatic niche formation in colorectal cancer, suggesting that exosomal components are pivotal in the metastatic process (ref: Li doi.org/10.1186/s13046-024-02991-3/). Additionally, the infiltration of granulocytic myeloid-derived suppressor cells (gMDSCs) into the lung premetastatic niche has been linked to osteosarcoma, indicating that exosome-mediated communication between tumor cells and the microenvironment is crucial for metastasis (ref: Deng doi.org/10.1016/j.celrep.2024.113751/). The interplay between exosomes and immune cells, particularly MDSCs, highlights the potential for targeting these pathways to improve cancer immunotherapy outcomes (ref: Zhao doi.org/10.1186/s13045-024-01529-6/). Furthermore, the role of circulating tumor DNA (ctDNA) in monitoring treatment response and disease progression has been emphasized, with studies showing its association with clinical outcomes in various cancers (ref: Tan doi.org/10.1002/cncr.35263/). These findings collectively underscore the significance of understanding cancer metastasis and the tumor microenvironment in developing effective therapeutic strategies.