The tumor microenvironment (TME) plays a crucial role in cancer progression and metastasis, as evidenced by recent studies. One significant finding is that stromal lipids, particularly phosphatidylcholines from young subcutaneous adipocytes, are taken up by melanoma cells, enhancing their PI3K-AKT signaling and oxidative phosphorylation (OXPHOS). This metabolic shift leads to increased oxidative stress, which paradoxically reduces metastatic burden. Notably, high OXPHOS melanoma cells tend to metastasize to the lung and brain, while antioxidant treatment can shift this tropism towards the liver (ref: Gurung doi.org/10.1016/j.ccell.2025.04.001/). Furthermore, a comprehensive analysis of brain metastases (BrMs) using single-cell RNA sequencing on 108 BrM samples revealed the complexity of cellular states and compositions across various cancer lineages, highlighting the need for more refined profiling to understand BrM better (ref: Xing doi.org/10.1016/j.ccell.2025.03.025/). Additionally, the role of circulating tumor DNA (ctDNA) clearance as a predictive biomarker for pathologic complete response (pCR) in patients undergoing neoadjuvant immune checkpoint inhibitors was assessed through a systematic review and meta-analysis, demonstrating a high pooled sensitivity of 0.98, although specificity was lower at 0.53 (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/).

Immunotherapy has emerged as a promising approach in treating various cancers, particularly glioblastoma. A recent study comparing nivolumab combined with radiotherapy and temozolomide against a placebo arm showed 12-month overall survival (OS) rates of 82.7% and 87.7%, respectively, with a notable difference in patients not on corticosteroids (85.5% vs. 89.9%) (ref: Ellenbogen doi.org/10.1038/s41591-025-03607-9/). This highlights the potential of immunotherapy in enhancing survival outcomes. In the context of circulating tumor DNA (ctDNA), its clearance has been identified as a significant predictor of pCR in patients treated with neoadjuvant immune checkpoint inhibitors, with a diagnostic odds ratio of 57.36, indicating its utility in clinical settings (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). Moreover, a phase Ib study combining ibrutinib, lenalidomide, and rituximab for relapsed/refractory CNS lymphoma showed promising results, with one-third of patients achieving durable responses exceeding 12 months, suggesting that combination therapies may enhance treatment efficacy (ref: Schaff doi.org/10.1093/neuonc/).

Genetic and epigenetic alterations are pivotal in tumorigenesis, as demonstrated in recent studies. A pan-cancer analysis of brain metastases utilized single-cell RNA sequencing to investigate the cellular composition and states across different cancer types, revealing significant insights into the remodeling processes that occur during metastasis (ref: Xing doi.org/10.1016/j.ccell.2025.03.025/). Additionally, the ACHILLES/TORG1834 trial compared afatinib to chemotherapy in patients with non-small cell lung cancer harboring uncommon EGFR mutations. The interim analysis indicated that patients receiving afatinib had a median progression-free survival (PFS) of 10.6 months, significantly longer than those on chemotherapy, suggesting that afatinib may serve as a new standard of care for this patient population (ref: Miura doi.org/10.1200/JCO-24-02007/). These findings underscore the importance of understanding genetic variations and their implications for targeted therapies.

Novel therapeutic strategies are essential for overcoming drug resistance in cancer treatment. The ATM inhibitor WSD0628 has shown promise in enhancing radiosensitization of glioblastoma and brain metastases, specifically designed for effective distribution across the blood-brain barrier. In patient-derived xenograft models, WSD0628 demonstrated significant inhibition of the DNA damage response, suggesting its potential as a therapeutic agent in combination with radiation therapy (ref: Xue doi.org/10.1093/neuonc/). Furthermore, the role of B cell-derived acetylcholine in liver regeneration highlights the interplay between immune signaling and tissue recovery, indicating that neurotransmitters may have therapeutic implications in regenerative medicine (ref: Modares doi.org/10.1016/j.immuni.2025.04.002/). These studies emphasize the need for innovative approaches to address the challenges of drug resistance and enhance therapeutic efficacy.

The identification of reliable biomarkers is crucial for improving cancer treatment outcomes. A systematic review and meta-analysis on ctDNA clearance as a predictive biomarker for pCR in patients treated with neoadjuvant immune checkpoint inhibitors revealed a high pooled sensitivity of 0.98, although the specificity was lower at 0.53, indicating its potential utility in clinical practice (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). Additionally, genome-wide association studies (GWAS) identified 25 genetic risk loci associated with infertility, providing insights into reproductive traits and their genetic underpinnings. However, the lack of correlation between female infertility and reproductive hormones suggests a complex interplay of factors influencing fertility (ref: Venkatesh doi.org/10.1038/s41588-025-02156-8/). These findings highlight the importance of integrating genetic insights into predictive models for personalized medicine.

Clinical trials are essential for evaluating new therapies and their impact on patient outcomes. The systematic review on ctDNA clearance as a predictive biomarker for pCR in solid tumors treated with neoadjuvant immune checkpoint inhibitors demonstrated significant findings, with a diagnostic odds ratio of 57.36, emphasizing the importance of ctDNA in predicting treatment responses (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). In the context of glioblastoma, the NIVO + RT + TMZ regimen showed promising 12-month OS rates, particularly in patients without corticosteroid use, indicating the potential for improved survival outcomes with immunotherapy (ref: Ellenbogen doi.org/10.1038/s41591-025-03607-9/). These studies underscore the critical role of clinical trials in shaping treatment paradigms and enhancing patient care.

Neuro-oncology continues to evolve with insights into brain tumors and metastases. The pan-cancer brain metastases atlas, utilizing single-cell RNA sequencing, provided a comprehensive overview of the cellular landscape in brain metastases, revealing important characteristics and remodeling processes that could inform future therapeutic strategies (ref: Xing doi.org/10.1016/j.ccell.2025.03.025/). Additionally, the role of ctDNA clearance as a predictive biomarker for pCR in solid tumors treated with neoadjuvant immune checkpoint inhibitors highlights its relevance in neuro-oncology, where treatment responses can be challenging to assess (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). These findings emphasize the need for continued research in understanding brain tumors and improving patient outcomes through targeted therapies.

Neuroinflammation is increasingly recognized as a critical factor in cancer progression and treatment responses. The systematic review on ctDNA clearance as a predictive biomarker for pCR in patients treated with neoadjuvant immune checkpoint inhibitors revealed a high pooled sensitivity, underscoring its potential role in monitoring treatment efficacy (ref: Valenza doi.org/10.1016/j.annonc.2025.03.019/). Moreover, the GWAS identifying 25 genetic loci related to infertility also highlights the complex interplay between genetic factors and neurological outcomes, suggesting that understanding these relationships could inform future therapeutic strategies (ref: Venkatesh doi.org/10.1038/s41588-025-02156-8/). These studies illustrate the importance of integrating neuroinflammatory mechanisms into cancer research to enhance treatment approaches.