Advances in cancer research最新文献

Treatment of brain metastasis has traditionally included surgical resection for single lesions in accessible locations. However, multiple lesions, small size, location within deeper structures or need for transgression of eloquent cortex renders surgical resection a less viable option. Stereotactic radiosurgery and whole brain radiation are additional treatment options, however risks of worsening neurocognitive symptoms, post-radiation edema, and most significant, radiation necrosis are apparent. With advances in minimally invasive laser delivery systems and magnetic resonance imaging, laser interstitial thermal therapy (LITT) has become an increasingly popular option for brain metastasis and radiation necrosis. This chapter will review the history and physics of LITT, discuss pioneering cases which pushed the boundaries of this therapy, and seminal trials which have explored its efficacy in treating brain metastasis and radiation necrosis.

The modern treatment of both high and low-grade glioma involves achieving a maximum resection of radiographically visible as well as occult infiltrative tissue without sacrificing neurologic function. To this end, several intraoperative imaging adjuncts have been developed including translation of traditional imaging tools such as MRI, CT scan, and ultrasonography to the operating room. Novel techniques in glioma surgery include fluorescence guided surgery which takes advantage of cellular differences to illuminate tumor tissue and allow for easier differentiation. Future intraoperative imaging techniques are focused on identifying histopathologic differences between tumor and normal brain to maximize the identification of infiltrative tissue that is otherwise not visible with existing techniques. In this chapter we will describe the advantages and disadvantages of each of these techniques and describe how each can be used in the modern neurosurgeon's armamentarium.

New strategies and mechanisms for managing and treating cancer are essential; a novel therapeutic approach has now emerged in the scope of targeted protein degradation called Proteolysis-Targeting Chimeras (PROTACs). This technology specifically targets and degrades disease-causing proteins via the ubiquitin-proteasome system, leading to expanded research in both academia and industry over the past two decades. The diversity of PROTAC classes based on the E3 ligase recruiting ligand and the target protein allows for a universal molecular structure that can be tailored for a specific target. As such, PROTACs have been widely evaluated across a multitude of cancer variants and reported to effectively target a wide range of proteins across multiple cellular pathways. Overall, the ability of PROTAC technology to degrade both 'druggable' and 'undruggable' targets has resulted in a rapid expansion of research in the brief time since its initial discovery. Continued intense efforts will help further shape this evolving field of 'dynamic protein management' to transition PROTACs into clinical settings.

In the Summer of 2021 the World Health Organization (WHO) issued a reclassification of central nervous system (CNS) malignancies, which would ultimately change how adult gliomas would be defined, classified, and treated. The 2021 update emphasized molecular diagnostics in its reclassification of tumors, while also staying true to prior incorporation of both histology and immunohistochemistry. This chapter will summarize these definitions, epidemiology, work-up, and management of adult diffuse gliomas with an emphasis on radiotherapy (RT) treatment planning.

Pediatric high-grade gliomas (pHGGs) and diffuse midline gliomas (DMGs) represent some of the most aggressive and lethal childhood brain tumors. Recent molecular and epigenetic discoveries have redefined these entities as distinct from adult gliomas, with hallmark alterations such as H3K27M and H3G34R/V mutation driving unique biological behaviors. Advances in genomic, epigenomic, and transcriptomic profiling have enabled refined diagnostic classifications, improved our understanding of tumor heterogeneity, and revealed novel therapeutic targets. Despite these insights, standard of care approaches-primarily radiotherapy-remain palliative and conventional chemotherapy has shown limited efficacy. Emerging strategies, including targeted molecular therapies, immunotherapies, and innovative drug delivery techniques, offer promise but face significant challenges related to blood-brain barrier integrity, immune evasion, and intratumoral heterogeneity. Integration of DNA methylation profiling, enhancer landscape analysis, and liquid biopsy technologies are transforming diagnostic and monitoring capabilities. Future progress will depend on interdisciplinary collaboration, the development of predictive preclinical models, multi-omic integration, and adaptive clinical trial designs. Ultimately, tackling the biological complexity of pHGGs and DMGs through personalized, molecularly targeted approaches offers the best hope for improving outcomes in this devastating disease group.

Recent advancements in the molecular understanding of pediatric brain tumor biology have significantly contributed to the development of innovative therapeutic strategies aimed at improving clinical outcomes for affected children. These scientific breakthroughs have facilitated the identification of specific molecular targets and signaling pathways integral to the oncogenesis of pediatric brain tumors, thereby enabling the design of targeted therapies that disrupt these pathogenic processes. Furthermore, the incorporation of immunotherapy and precision medicine approaches has unveiled novel therapeutic avenues, offering the potential for more efficacious and less toxic treatment modalities. As research in this domain continues to progress, these cutting-edge therapeutic interventions are anticipated to enhance survival rates and improve the quality of life for pediatric patients. This review delineates emerging interventional treatments in pediatric brain tumor management and examines the persistent challenges within the field.

Medulloblastoma (MB) stands out as the most prevalent, invasive, and biologically heterogeneous pediatric brain tumor. MB accounts for almost 1/4th of all intracranial neoplasms. The prime age of diagnosis is 5-9 years of age; however, the disease is also seen at a later age in approximately 25 % adults. The standard treatment for the disease is comprised of multimodal approaches incorporating surgery, radiation therapy, and adjuvant chemotherapy, which increases the survival to 70-80 %. Despite considerable progress in therapies and novel drug discoveries, 30 % of the survivors succumb to lifelong morbidities and chronic disabilities. A deeper understanding of the disease's molecular landscape has led to the identification of four distinct molecular subgroups: wingless (WNT), sonic hedgehog (SHH), Group 3 and Group 4. This classification, coupled with clinical-pathological assessments of the disease, has enhanced the search for more targeted and effective therapies for MB. In this review, we present an overview of MB, with an emphasis on current treatment options and challenges, utilization of molecular subgroup-specific genetic alterations in development of targeted therapies, including immunotherapy. Additionally, emerging nanomedicine approaches aimed at overcoming the inefficient blood brain barrier (BBB) penetration of drugs used for the treatment of MB, are discussed.

Breast cancer remains the most frequently diagnosed cancer and a leading cause of cancer-related mortality in women globally. While genetic mutations are well-established contributors to breast cancer pathogenesis, accumulating evidence underscores the pivotal role of epigenetic dysregulation including DNA methylation, histone modifications, and non-coding RNAs in driving tumor initiation, progression, metastasis, and therapeutic resistance. These reversible modifications regulate gene expression and chromatin structure without altering the underlying DNA sequence, offering unique opportunities for biomarker discovery and targeted intervention. This review provides a comprehensive overview of the epigenetic landscape in breast cancer, highlighting key molecular players such as BRCA1, RASSF1A, CDH1, and SOX17, and detailing the roles of histone acetylation, methylation, and phosphorylation in chromatin remodeling and gene regulation. The contributions of microRNAs and long non-coding RNAs in modulating cancer phenotypes and therapy responses are also discussed. Furthermore, we explore emerging epigenetic therapies ("epidrugs"), their integration with standard chemotherapy and immunotherapy, and the potential of multi-omics approaches in precision oncology. By linking molecular insights to clinical applications, this review emphasizes the promise of epigenetic strategies in advancing personalized treatment for breast cancer patients.

Prostate cancer (PCa) is the most common non-skin cancer among men in the United States. However, the widely used protein biomarker in PCa, prostate-specific antigen (PSA), while useful for initial detection, its use alone cannot detect aggressive PCa and can lead to overtreatment. This chapter provides an overview of PCa protein biomarker development. It reviews the state-of-the-art liquid chromatography-mass spectrometry-based proteomics technologies for PCa biomarker development, such as enhancing the detection sensitivity of low-abundance proteins through antibody-based or antibody-independent protein/peptide enrichment, enriching post-translational modifications such as glycosylation as well as information-rich extracellular vesicles, and increasing accuracy and throughput using advanced data acquisition methodologies. This chapter also summarizes recent PCa biomarker validation studies that applied those techniques in diverse specimen types, including cell lines, tissues, proximal fluids, urine, and blood, developing novel protein biomarkers for various clinical applications, including early detection and diagnosis, prognosis, and therapeutic intervention of PCa.

Worldwide, prostate cancer (PCa) remains a leading cause of death in men. Histologically, the majority of PCa cases are classified as adenocarcinomas, which are mainly composed of androgen receptor-positive luminal cells. PCa is initially driven by the androgen receptor axis, where androgen-mediated activation of the receptor is one of the primary culprits for disease progression. Therefore, in advanced stage PCa, patients are generally treated with androgen deprivation therapies alone or in combination with androgen receptor pathway inhibitors. However, after an initial decrease, the cancer recurs for majority patients. At this stage, cancer is known as castration-resistant prostate cancer (CRPC). Majority of CRPC tumors still depend on androgen receptor axis for its progression to metastasis. However, in around 20-30% of cases, CRPC progresses via an androgen receptor-independent pathway and is often presented as neuroendocrine cancer (NE). This NE phenotype is highly aggressive with poor overall survival as compared to CRPC adenocarcinoma. NE cancers are resistant to standard taxane chemotherapies, which are often used to treat metastatic disease. Pathologically and morphologically, NE cancers are highly diverse and often co-exist with adenocarcinoma. Due to the lack of proper biomarkers, it is often difficult to make an early diagnosis of this lethal disease. Moreover, increased tumor heterogeneity and admixtures of adeno and NE subtypes in the same tumor make early detection of NE tumors very difficult. With the advancement of our knowledge and sequencing technology, we are now able to better understand the molecular mediators of this transformation pathway. This current study will give an update on how various molecular regulators are involved in these lineage transformation processes and what challenges we are still facing to detect and treat this cancer.