Advances in cancer research最新文献

Cerebrospinal fluid (CSF) circulates in the ventricular system and subarachnoid space, and through its interaction with interstitial fluid, facilitates nutrient and waste exchange to support the functional needs of cells in the brain and spinal cord. In the setting of primary brain tumors, CSF has been implicated in tumor pathogenesis by serving as both a reservoir and vehicle for factors which may support tumor progression, therefore contributing to the tumor microenvironment. Pathological manifestations of CSF in the setting of brain tumors include hydrocephalus due to tumor obstruction of CSF pathways, CSF seeding and leptomeningeal metastasis, and transependymal flow. CSF also has roles as a reservoir for biomarkers important in brain tumor detection and as a site for direct delivery of therapeutic agents to bypass the blood brain barrier. Despite the intimate association between CSF and brain tumors, few studies have investigated mechanisms of local and global alterations of fluid flow in the setting of glioma, the most common malignant primary brain tumor in the central nervous system. Here, we provide an overview of recent advances in our understanding of the roles, implications, regulations, and diagnostic/therapeutic implications of CSF in glioma and how they may be leveraged for research and clinical application.

The diagnosis of primary brain tumors at presentation and with progression presents unique challenges, in part due to the inherent risks and limitations of neurosurgical sampling. Emerging liquid biopsy techniques analyzing circulating tumor DNA (ctDNA) in the cerebrospinal fluid (CSF) are potentially revolutionary, affording a minimally invasive means of collecting valuable tumor-related information. Here we review the most salient factors contributing to successful detection of CSF ctDNA, the most developed ctDNA assay techniques and the clinical contexts in which CSF liquid biopsy has been applied. Future opportunities for liquid biopsy advancement are also explored. Integration of these techniques into routine clinical care will require rigorous validation through clinical trials and standardization of assay pipelines but holds great promise for the future of neuro-oncology.

Molecular profiling has revolutionized the diagnosis, classification, and treatment of various cancers, with advances in next-generation sequencing and DNA methylation profiling offering unprecedented insights into tumor biology. This paradigm shift has enhanced the understanding of driver mutations in cancers translating into improved patient outcomes. In primary brain tumors, particularly gliomas, molecular profiling has redefined classification frameworks, yet meaningful improvements in patient survival remain elusive, particularly for glioblastoma. However, recent strides in molecularly targeted therapies have led to landmark FDA approvals, including agents such as vorasidenib for IDH-mutant gliomas, the combination of dabrafenib trametinib for BRAF mutated tumors, and TRK inhibitors for NTRK fusion-positive tumors. While conventional treatments like surgery, radiation, and chemotherapy remain the standard of care for gliomas, the integration of molecular-driven therapies is beginning to shape clinical management strategies. This article explores the evolving role of molecularly targeted treatments in adult primary brain tumors, examining their current applications and future potential.

Mitochondria are major sites of ATP production, also serving as metabolic and biosynthetic hubs. The structure of mitochondria comprises a matrix enclosed by an inner membrane which is separated from the outer mitochondrial membrane (OMM) by the intermembrane space. The OMM is a lipid bilayer that forms an interphase between mitochondria and the surrounding cytosol. While its primary function is to act as a selective barrier, controlling the exchange of molecules between these two cellular compartments, the OMM also plays a crucial role in various metabolic and regulatory processes. It is home to 114 distinct proteins, including transporters, signaling molecules, and structural components. Among these, approximately 30 are enzymes that actively participate in the regulation of lipid metabolism, amino acid processing, calcium homeostasis, and heme biosynthesis. These enzymatic functions highlight the OMM's significance beyond its structural role, positioning it as a key player in cellular energy balance, apoptosis, and intracellular signaling pathways. Here, we focus on OMM proteins involved in the synthesis and utilization of cholesterol and fatty acids. We describe the mechanisms of action, effects, regulation, association with cancer progression, and their potential as pharmacological targets of the steroid acute regulatory protein (StAR), translocator protein (TSPO), acetyl-CoA carboxylase β (ACCβ), acyl-CoA synthetases long chain family member 1 and 6 (ACSL1 and ACSL6), and carnitine palmitoyl transferases 1A and 1B (CPT1A and CPT1B). Overall, we provide a comprehensive view of these OMM enzymes in non-cancerous and cancer cells as well as their potential as targets for developing novel chemotherapies.

Pediatric-type diffuse low grade glioma are a novel subgrouping of pediatric glioma defined in the updated WHO 2021 classification of central nervous system tumors. The newly recognized pediatric-type diffuse low grade glioma family is comprised of four distinct entities, including diffuse astrocytoma MYB or MYBL1-altered, angiocentric glioma, polymorphous low-grade neuroepithelial tumor of the young, and diffuse low grade glioma MAPK-altered. Due to significant overlap in histopathology and molecular alterations between pediatric-type diffuse low grade glioma, accurate diagnosis of these tumor subtypes requires integration of both histology and molecular findings. Herein, we describe the epidemiologic, imaging, and molecular features of these pediatric diffuse glioma. In addition, we review current knowledge regarding management approach and treatment outcomes, including potential therapeutic implications of prevalent molecular alterations within this family of tumors.

Cell adhesion molecules (CAMs) mediate cellular adhesions to neighboring cells and the extracellular matrix (ECM) to regulate tissue homeostasis and morphogenesis. Dysfunctional CAM-mediated signaling is required for a neoplastic cell to gain an invasive and metastatic phenotype. Numerous studies have reported a dynamic plasticity in the function and expression of CAMs that regulates the different stages of tumor progression. As such, CAM-induced changes in cell adhesion and intracellular signaling enable phenotype switching and cellular plasticity in cancer cells that contribute to tumor aggressiveness and metastasis. This review summarizes the properties of cell adhesion molecules and the signaling pathways involved in regulating tumor progression and metastasis.

Central Nervous System (CNS) germinomas are rare, malignant germ cell tumors that predominantly affect children, adolescents and young adults (AYA). These tumors are highly sensitive to irradiation and chemotherapy, making them one of the most curable intracranial malignancies. This review provides a comprehensive overview of germinoma, covering epidemiology, pathogenesis, clinical presentation, diagnostic approaches, treatment strategies, and long-term outcomes. We also discuss recent advances in molecular biology and their implications on future therapeutic developments.

The treatment of human cancer has shifted toward a precision-medicine paradigm that increasingly relies on the genomic annotation of each patient's tumor tissue. This trend is supported by the observation that treatment response is often dependent on tumor mutations in targeted pathways, by the discovery of particular drug-resistance mutations in tumors that resume growth during therapy, and by the recent association between effective immunotherapy and tumor-specific missense mutations. Early detection of cancer and accurate characterization of tumors improve patient outcomes, so research into noninvasive means of obtaining this information is of significant clinical relevance. Furthermore, the outgrowth of drug-resistant tumor cell clones during therapy can limit the clinical relevance of the initial tumor profile and has motivated the development of technologies that can track the evolution of the cancer genome in accessible body fluids.

Introduction Adamantinomatous craniopharyngioma (ACP) is a significant source of morbidity in the pediatric brain tumor population. It predominantly arises from the parasellar space. The tumors proximity to key vital structures often makes gross total surgical resection challenging and sometimes clinically inadvisable. Compounding the problem, adjunct therapies are not yet capable of providing a definitive cure. Recent preclinical research has made significant progress towards elucidating the mutagenic drivers of ACP, however much work remains to translate this into safe and effective treatments. Content Overview and Key Takeaways In the following chapter, we discuss the most up-to-date understanding of ACP biology and management. ACP is a histologically low grade tumor characterized by a mutation involving the beta-catenin protein, resulting in pathologic stability of the protein that impairs cell death or apoptosis. A subpopulation of tumor cells then enter a transcriptomic state characterized by cellular oncogenic senescence. It is unclear how this state leads to feed forward loops resulting in tumorigenesis. Despite its benign nature, the consistent anatomic origin of ACP in the sellar/suprasellar space, often abutting or involving the hypothalamus, the infundibulum, and the optic chiasm, contributes to multiple long-term complications such as endocrinopathies, obesity, vision loss, and obstructive hydrocephalus. Surgically, the current trend is towards conservative approaches with the goal of maximal safe resection without perturbing the hypothalamus. Adjunct radiotherapy is standard in cases of residual or recurrent disease. Close coordination with endocrinology colleagues is vital to appropriately care for these patients as they often suffer from lifelong endocrinopathies that remain a significant source of burden in this population.