Advances in cancer research最新文献

Astrocyte elevated gene-1 (AEG-1), also known as metadherin (MTDH), has emerged as a multifunctional oncogene implicated in cancer progression, metastasis, immune evasion, and notably, drug resistance across diverse malignancies. AEG-1 exerts its effects by modulating key signaling cascades, including PI3K/Akt, NF-κB, and Wnt/β-catenin, and by regulating genes associated with epithelial-mesenchymal transition, apoptosis suppression, cancer stemness, and multidrug resistance. Its interactions with molecular partners such as SND1, USP10, and nucleolin further amplify its oncogenic potential, especially in immune suppression and therapy resistance. This review provides a comprehensive overview of AEG-1-mediated drug resistance mechanisms across tumor types including breast, liver, lung, glioma, and gynecological cancers. Tumor-specific signaling contexts and immune microenvironmental interactions are examined to highlight how they shape AEG-1 function. Therapeutic challenges in targeting AEG-1-such as its non-enzymatic structure and intracellular localization-are critically discussed. We further explore emerging strategies to inhibit AEG-1, including RNA interference, long noncoding RNA modulation, partner interaction disruption, phytochemical inhibitors, and nanoparticle-based delivery systems. AEG-1 is also evaluated as a prognostic and predictive biomarker with translational relevance in precision oncology. Future studies should prioritize its integration into biomarker-guided clinical trials and the development of tumor-specific AEG-1-targeted therapies. This review underscores AEG-1 as a central mediator of drug resistance and a compelling target for next-generation cancer therapeutics.

Glioblastoma (GBM) accounts for 52 % of all malignant primary brain tumors. The main treatment regimens include surgical resection followed by chemoradiotherapy. Despite these, the median survival of patients with GBM is only 15 months. To make things worse the neuroimaging characteristics mimic tumor recurrence. Traditional static Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is also unreliable. In this review manuscript we describe advanced PET methods to differentiate tumor progression (TP) from treatment related necrosis (TN) in post treated GBM patients. Dynamic FDG PET (dPET), an advance from traditional static FDG PET, may prove advantageous in clinical staging. Quantifying dPET data is however challenging. In this review we showcase new work for an end-to-end novel AI platform for automated blood input computation to quantify dPET data. Next, we review new work on a large AI model for multimodal brain tumor segmentation from post-treated BraTS2024 MRI datasets and finally a multi-modal AI platform including dPET and MRI for classification of TP vs TN.

Non-germinomatous germ cell tumors (NGGCTs) are rare, histologically diverse malignancies that primarily affect children and adolescents. Unlike germinomas, NGGCTs are less responsive to chemotherapy and radiation, resulting in a less favorable prognosis and necessitating intensified multimodal therapy. This chapter provides a comprehensive overview of NGGCTs, including histological subtypes, clinical presentation, diagnostic strategies, and established as well as emerging treatment paradigms. We discuss current classification systems, the roles of tumor markers and neuroimaging, and challenges in histopathologic diagnosis. Treatment approaches vary globally but typically include intensive chemotherapy combined with craniospinal or whole-ventricular irradiation. Long-term outcomes remain suboptimal for high-risk subtypes, especially those with yolk sac tumor, choriocarcinoma or embryonal carcinoma components. Recent genomic and epigenomic studies have revealed recurrent alterations in the RTK/MAPK and PI3K/mTOR pathways, along with distinctive methylation signatures and copy number aberrations, offering insights into tumorigenesis and potential therapeutic targets. Ongoing trials continue to focus on refining risk stratification and minimizing treatment-related toxicities. These efforts, along with advances in molecular characterization, may ultimately improve survival and long-term quality of life in patients with CNS NGGCTs.

Medulloblastoma, once considered a uniform entity, is now accepted as a complex and heterogeneous group of tumors requiring a nuanced and multidisciplinary approach to diagnosis and treatment. The now four recognized primary subgroups have distinct genetic, epigenetic, and clinical characteristics that influence prognosis and treatment responses necessitating subgroup-specific strategies. Advances in diagnostics and risk stratification, largely driven by a deeper understanding in tumor biology, has led to an overall improvement in survival (>70 %), through risk-adapted treatment strategies. Contemporary clinical approaches incorporate a multimodality treatment strategy, integrating surgery, radiotherapy and intensive chemotherapy, each of which is associated with significant short- and long-term morbidity. Novel targeted therapeutics continue to be developed, investigated and explored in vitro, in vivo and through clinical trial design, particularly in the high risk and relapsed settings. As the therapeutic landscape continues to evolve, combining conventional therapies with these approaches holds promise to improve clinical outcomes. These innovations and developments expanding all disciplines aim to continue to provide precision-based care and enhance survival outcomes across all subgroups whilst mitigating the significant long-term burden of treatment-related sequelae disproportionately experienced by medulloblastoma survivors.

Pediatric central nervous system (CNS) tumors are the most common solid tumors in children and remain the leading cause of death amongst childhood cancer patients. Despite the intensity of standard cytotoxic regimens, many patients with high-grade tumors still experience relapse, at which time they have limited curative options. Even the survivors of childhood CNS tumors are often left with lifelong complications that negatively impact their quality of life. Immunotherapy holds the promise of tailored therapies that can improve outcomes and inflict fewer side effects. Early successes across against leukemia and some solid tumors have supported this promise, but this is only the infancy of targeted immunotherapies against pediatric CNS tumors. While this is a new, blossoming field, a robust and coordinated preclinical environment has spurred a spectrum of innovative clinical trials that serve as the ground floor for these new technologies. Here, we will review the current state of cellular therapy, immune checkpoint inhibition, cancer vaccines, and oncolytic viral therapy for children with CNS tumors.

Over the past 30 years, advancements in radiotherapy have transformed the treatment of pediatric ependymoma, improving tumor control and reducing treatment-related complications. Early protocols, such as RT1 and ACNS0121, demonstrated the efficacy of immediate post-operative radiotherapy, particularly for children as young as 12 months, setting benchmarks for modern treatment strategies. The introduction of conformal photon therapy revolutionized tumor targeting by minimizing radiation exposure to surrounding normal tissues, while proton therapy has emerged as the preferred modality in developed countries due to its superior normal tissue-sparing properties. Despite these advances, long-term comparative data between photon and proton therapy remains limited. Critical factors in radiotherapy planning include tumor location, patient age, molecular features, and the potential for neuraxis dissemination. Advances in imaging, such as high-resolution MRI and emerging molecular staging techniques, have enhanced precision in treatment planning and risk stratification. However, challenges persist for patients with residual or recurrent disease. Reirradiation has emerged as a promising option for relapse, demonstrating high rates of tumor control and low risks of complications when combined with timely surgical intervention and multidisciplinary care. This chapter highlights the importance of leveraging data from three separate clinical trials to refine treatment strategies and address cognitive outcomes, which have been identified as a major area of clinical importance and research. Future trials are expected to explore molecular risk stratification and the integration of systemic therapies alongside radiotherapy to optimize outcomes, ensuring continued progress in the care of children with ependymoma.

Brain metastases (BMs) affect approximately 10-30 % of cancer patients, and their prevalence is growing as patients live longer with controlled primary disease. Surgical resection remains a cornerstone of treatment for both solitary and multifocal lesions. Since the advent of intracranial tumor surgery, neurosurgery has trended towards less invasive surgical approaches, facilitated by a proliferation of surgical innovations ranging from intraoperative MRI to tubular retractors. Minimally invasive cranial surgery (MICS) incorporates approaches such as keyhole craniotomies and tubular retraction with the goal of maximizing extent of resection and reducing iatrogenic tissue injury. Supramarginal resection builds upon this approach, expanding the boundaries of the resection cavity to ensure removal of microscopic tumor fragments and decrease recurrence. Because MICS is generally performed through craniotomies< 5 cm in diameter with limited ability to change predefined surgical corridors intraoperatively, meticulous attention must be given to the preoperative workup. Imaging modalities, including CT, MRI, DWI, and DTI, may reveal characteristics of the intra-tumoral environment and are important in defining the anatomical relationship of BMs to surrounding functional tissue and neurovascular structures. Intraoperatively, neuronavigation helps maintain alignment within predefined surgical corridors, and adjunctive modalities such as intraoperative ultrasound and brain mapping help compensate for brain shift. Advancements in visual augmentation tools such as fluorescence, endoscopes, and exoscopes further enable intraoperative delineation of tumor boundaries and allow for expanded utilization of MICS in deep-seated, complex BMs. The ever-growing armamentarium of minimally invasive surgical tools has made neurosurgery an increasingly safe and effective option for patients with BMs.

Human development of the blood-brain-barrier - a semi-permeable membrane that both separates and protects the brain and spinal cord from potential toxins coursing through the human circulatory system, while simultaneously permitting oxygen and nutrient delivery - also lead to the creation of the largest sanctuary site for malignancy in the human body: the central nervous system (CNS) . The most commonly used cocktails of chemotherapeutic treatments are unable to breach the blood-brain-barrier and treat metastatic cancer cells seeking asylum behind its walls, and other sanctuary sites (e.g. genital tract, testicles, placenta and umbilical cord in pregnancy, etc.). As a result, therapies that are unobstructed by the blood-brain-barrier are of paramount importance when treating CNS metastases. Radiation therapy (RT) is among these commonly employed modalities and can be used as both a first line treatment and, in some cases, as prophylaxis against microscopic disease armed with the potential to mature into symptomatic cerebral metastases.

Brain metastases (BrM) and leptomeningeal metastases (LM) are increasingly common neurologic complications of cancer. The era of precision oncology has ushered in a deeper understanding of the molecular alterations that drive oncogenesis, subsequently informing and accelerating the drug development process. New systemic treatments, including oral tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) as well as antibody-drug conjugates (ADCs), have substantial intracranial efficacy with meaningful clinical benefit for BrM patients. Our understanding of LM continues to evolve with the development of improved detection methods and an increasing number of brain penetrant therapies. Targeted therapeutics continue to transform the existing treatment landscape and add both choice and complexity to the clinician's calculus when managing patients with BrM and/or LM. Multidisciplinary discussion should ultimately guide all treatment decisions and explore both the benefits and toxicities of various therapy options. Systemic targeted therapies should be considered for patients with asymptomatic or minimally symptomatic small BrM and/or LM. Future studies investigating treatment timing and effective combinatorial strategies are urgently needed.

Brain metastases are the most common intracranial malignancies in adults, and, depending on primary tumor type, they may affect up to 50 % of cancer patients. Although advances in systemic and local therapies have led to improvements in patient overall survival and progression free survival, there remains substantial opportunities to improve patient outcomes. Stereotactic radiosurgery (SRS) delivers high doses of ionizing radiation with sub-millimeter accuracy to discrete intracranial tumors. It has emerged as the standard of care for patients with limited number of brain metastases, and it serves as a valuable adjuvant after resection. Moreover, SRS is typically seamlessly integrated into systemic therapy treatment regimens. Continued improvement in SRS technology and growing evidence have led to expansion of SRS indications and introduction of new SRS techniques. Frameless SRS technologies have allowed for treatment of larger lesions and even lesions adjacent to critical structures for which single session SRS would not be prudent. Neoadjuvant SRS has recently been proposed as an alternative to adjuvant SRS and appears to help reduce the risk of leptomeningeal dissemination. These novel SRS techniques require further evaluation through prospective clinical trials and registry based studies. In addition, the concurrent combination of systemic therapies with central nervous system (CNS) activity and SRS has yielded promising results with respect to local control and adverse radiation events rates. The concurrent delivery of SRS, precision medicine, and/or immunotherapy requires further refinements to fully optimize patient outcomes. In this review, we detail the current literature on established and forthcoming indications of SRS for brain metastases.