Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for monitoring cancer progression and treatment response. In a nationwide Danish cohort, Henriksen et al. demonstrated the clinical utility of ctDNA detection in colorectal cancer, highlighting the ability to adjust sensitivity and specificity of ctDNA tests based on clinical contexts, which could enhance personalized treatment strategies (ref: Henriksen doi.org/10.1016/j.annonc.2023.11.009/). Similarly, Tran et al. investigated ctDNA in early-stage non-small-cell lung cancer (NSCLC) and found that ctDNA detection, when combined with radiological tumor volume measurements, significantly improved predictions of relapse and overall survival among 85 patients who underwent surgical resection (ref: Tran doi.org/10.1016/j.annonc.2023.11.008/). In cervical cancer, Han et al. reported that persistent HPV ctDNA post-chemoradiation was associated with significantly worse progression-free survival (PFS), indicating its potential as an early marker for treatment response (ref: Han doi.org/10.1200/JCO.23.00954/). The landscape of ctDNA also includes insights into acquired resistance to targeted therapies. Bayle et al. found that up to 34% of patients exhibited alterations in ctDNA associated with secondary resistance, emphasizing the need for ongoing monitoring to adapt treatment plans (ref: Bayle doi.org/10.1186/s12943-023-01878-9/). Furthermore, Gimeno-Valiente et al. highlighted the importance of sequencing paired tumor DNA and white blood cells in localized colon cancer, revealing a 9% detection rate of pathogenic germline mutations, which could inform risk assessments for recurrence (ref: Gimeno-Valiente doi.org/10.1016/j.esmoop.2023.102051/). Collectively, these studies underscore the critical role of ctDNA in enhancing cancer monitoring and tailoring therapeutic approaches.

Liquid biopsy technologies have advanced significantly, providing non-invasive methods for cancer diagnosis and monitoring. Stoecklein et al. introduced an ultra-sensitive circulating tumor cell (CTC) detection method for pancreatic cancer, utilizing diagnostic leukapheresis to process large blood volumes. This approach allowed for the analysis of approximately 2.8 liters of blood, significantly improving the sensitivity of CTC detection in pancreatic adenocarcinoma (ref: Stoecklein doi.org/10.1186/s12943-023-01880-1/). In another study, Moss et al. explored the contributions of megakaryocytes and erythroblasts to circulating cell-free DNA (cfDNA), revealing that megakaryocytes account for about 26% of cfDNA in healthy individuals, which could enhance the interpretation of cfDNA-based assays (ref: Moss doi.org/10.1038/s41467-023-43310-2/). Moreover, the integration of immune profiling with liquid biopsy technologies has shown promise. Adamik et al. demonstrated that dendritic cell vaccine signatures correlate with overall survival in melanoma patients, linking metabolic profiles to immune responses (ref: Adamik doi.org/10.1038/s41467-023-42881-4/). Heger et al. developed a molecular prognostic index for central nervous system lymphomas, combining clinical risk factors with ctDNA assessment to improve risk stratification (ref: Heger doi.org/10.1182/blood.2023022020/). These advancements in liquid biopsy technologies not only enhance diagnostic capabilities but also pave the way for personalized treatment strategies based on individual tumor biology.

The identification of predictive biomarkers is crucial for optimizing cancer treatment strategies. Han et al. investigated the efficacy of a combination therapy involving a PD-L1 inhibitor and a VEGFR inhibitor in advanced triple-negative breast cancer (TNBC). They found that patients with low blood-based tumor mutational burden (bTMB) had significantly better responses and progression-free survival (PFS) compared to those with high bTMB, suggesting that bTMB can serve as a valuable predictive biomarker (ref: Han doi.org/10.1038/s41392-023-01672-5/). Similarly, Sharma et al. reported promising outcomes from a neoadjuvant regimen combining carboplatin, docetaxel, and pembrolizumab, indicating a high rate of pathological complete response (pCR) in TNBC patients, further supporting the role of biomarkers in guiding treatment decisions (ref: Sharma doi.org/10.1001/jamaoncol.2023.5033/). In the context of resistance mechanisms, Djureinovic et al. highlighted that higher doses of anti-CSF1R could lead to increased tumor growth and worse survival in preclinical models, suggesting that dosing strategies must be carefully considered to avoid adverse outcomes (ref: Djureinovic doi.org/10.1186/s12943-023-01884-x/). Additionally, Bayle et al. provided insights into the landscape of acquired resistance to targeted therapies, noting that alterations in ctDNA were observed in a significant proportion of patients, emphasizing the need for adaptive treatment approaches (ref: Bayle doi.org/10.1186/s12943-023-01878-9/). These findings collectively underscore the importance of integrating biomarkers into clinical practice to enhance treatment efficacy and patient outcomes.

Immunotherapy has revolutionized cancer treatment, but understanding resistance mechanisms remains a critical challenge. Han et al. identified predictive biomarkers for response to a combination of PD-L1 and VEGFR inhibitors in advanced TNBC, revealing that low blood-based tumor mutational burden (bTMB) and maximum somatic allele frequency (MSAF) were associated with improved treatment responses and longer PFS (ref: Han doi.org/10.1038/s41392-023-01672-5/). This highlights the potential of using genomic profiling to tailor immunotherapy strategies. In contrast, Djureinovic et al. demonstrated that higher doses of anti-CSF1R could lead to adverse outcomes in a murine model, suggesting that more aggressive dosing may not always translate to better therapeutic effects (ref: Djureinovic doi.org/10.1186/s12943-023-01884-x/). Furthermore, Heger et al. developed a molecular prognostic index for central nervous system lymphomas, integrating clinical risk factors with ctDNA assessment to enhance risk stratification and treatment personalization (ref: Heger doi.org/10.1182/blood.2023022020/). These studies collectively emphasize the importance of understanding both the predictive biomarkers and resistance mechanisms in immunotherapy, which can inform treatment decisions and improve patient outcomes.

Extracellular vesicles (EVs) are increasingly recognized for their role in cancer biology and as potential biomarkers. Eslami-S et al. investigated the prognostic value of circulating tumor cells (CTCs), ctDNA, and PD-L1-positive small extracellular vesicles in patients with metastatic non-small cell lung cancer (NSCLC). Their findings suggest that the combination of these liquid biopsy biomarkers can provide valuable prognostic information, enhancing the ability to predict patient outcomes (ref: Eslami-S doi.org/10.1038/s41416-023-02491-9/). This study underscores the potential of integrating multiple liquid biopsy modalities to improve prognostic accuracy in heterogeneous cancer populations. The interplay between EVs and the tumor microenvironment is also critical for understanding cancer progression. Research into the mechanisms by which EVs influence immune responses and tumor behavior is ongoing, with implications for therapeutic strategies. The ability to isolate and characterize EVs from patient samples could lead to novel insights into tumor biology and the development of targeted therapies, highlighting the need for further exploration in this area.

The development of novel therapeutics is essential for improving cancer treatment outcomes. Han et al. explored the combination of a PD-L1 inhibitor and a VEGFR inhibitor in advanced triple-negative breast cancer (TNBC), demonstrating that patients with low blood-based tumor mutational burden (bTMB) experienced significantly better responses and longer progression-free survival (PFS) (ref: Han doi.org/10.1038/s41392-023-01672-5/). This study emphasizes the importance of biomarker-driven approaches in optimizing treatment strategies. Similarly, Sharma et al. reported promising results from a neoadjuvant regimen combining carboplatin, docetaxel, and pembrolizumab, indicating a high rate of pathological complete response (pCR) in TNBC patients, which could lead to improved long-term outcomes (ref: Sharma doi.org/10.1001/jamaoncol.2023.5033/). In contrast, Djureinovic et al. highlighted the potential pitfalls of aggressive dosing in immunotherapy, showing that higher doses of anti-CSF1R could lead to increased tumor growth and worse survival in preclinical models (ref: Djureinovic doi.org/10.1186/s12943-023-01884-x/). This finding underscores the need for careful consideration of dosing strategies in the development of novel therapeutics. Collectively, these studies illustrate the dynamic landscape of cancer treatment, where innovative approaches and a deeper understanding of tumor biology are crucial for advancing patient care.