Biochimica et biophysica acta. Reviews on cancer最新文献

Histone deacetylases (HDACs) are key epigenetic regulators, and transcriptional complexes with deacetylase function are among the epigenetic corepressor complexes in the nucleus that target the epigenome. HDAC-bearing corepressor complexes such as the Sin3 complex, NuRD complex, CoREST complex, and SMRT/NCoR complex are common in biological systems. These complexes activate the otherwise inactive HDACs in a solitary state. HDAC complexes play vital roles in the regulation of key biological processes such as transcription, replication, and DNA repair. Moreover, deregulated HDAC complex function is implicated in human diseases including cancer. Therapeutic strategies targeting HDAC complexes are being sought actively. Thus, illustration of the nature and composition of HDAC complexes is vital to understanding the molecular basis of their functions under physiologic and pathologic conditions, and for designing targeted therapies. This review presents key aspects of large multiprotein HDAC-bearing complexes including their structure, function, regulatory mechanisms, implication in disease development, and role in therapeutics.

The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.

Glioblastoma (GBM), an extremely aggressive and prevalent malignant brain tumor, remains a challenge to treat. Despite a multimodality treatment approach, GBM recurrence remains inevitable, particularly with the emergence of temozolomide (TMZ) resistance and limited treatment options. Surprisingly, previous studies show that a history of allergies, atopy, or asthma is inversely associated with GBM risk. Further, the electronic medical record at the University Hospital of Lausanne showed that the GBM patients taking antihistamine during treatment had better survival. Histamine is an essential neurotransmitter in the brain and plays a significant role in regulating sleep, hormonal balance, and cognitive functions. Elevated levels of histamine and increased histamine receptor expression have been found in different tumors and their microenvironments, including GBM. High histamine 1 receptor (HRH1) expression is inversely related to overall and progression-free survival in GBM patients, further emphasizing the role of histamine in disease progression. This review aims to provide insights into the challenges of GBM treatment, the role of histamine in GBM progression, and the rationale for considering antihistamines as targeted therapy. The review concludes by encouraging further investigation into antihistamine mechanisms and their impact on the tumor microenvironment.

Thymic epithelial tumors (TETs) are rare neoplasms of the anterior mediastinum that arise from thymic epithelial cells. Although surgery is the preferred treatment for resectable TETs, the options for unresectable or recurrent advanced-stage TETs are limited beyond platinum-based chemotherapy. The evolving landscape of TET treatments is marked by significant advancements in targeted therapies and immunotherapies, particularly with anti-angiogenic agents and immune checkpoint inhibitors (ICIs). While monotherapies demonstrated certain efficacy, the development of combination strategies is vital for improving patient outcomes. This review consolidates progress in anti-angiogenic therapies and ICIs, emphasizing the evolution of combination therapies of TETs. Furtherly, we particularly discuss new first-line strategies based on these advancements and emphasizes exploring novel treatments like antibody-drug conjugates, immunomodulatory drugs and cytokine-based agents for TETs. Mechanistically, the molecular features of TETs integrated with clinical diagnosis and targeted therapy, and immunophenotyping of TETs along with its impact on the efficacy and safety of immunotherapy are discussed. Thus, this review systemizes the development in the treatment landscape of TETs, integrating the corresponding molecular and immune mechanisms, aiming to provide new references for the treatment of TETs.

Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as “genomic junk” to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including long interspersed element-1 (LINE-1), Alus, and long terminal repeat (LTR) elements, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.

Pancreatic ductal adenocarcinoma (PDAC) presents a significant therapeutic challenge as it is frequently diagnosed at advanced inoperable stages. Therefore, the development of a reliable screening tool for PDAC is crucial for effective prevention and treatment. Extracellular vesicles (EVs), characterized by their cup-shaped lipid bilayer structure and ubiquitous release from various cell types, offer notable advantages as an emerging liquid biopsy technique that is rapid, minimally invasive, easily sampled, and cost-effective. While EVs play a substantial role in cancer progression, EV proteins serve as direct mediators of diverse cellular behaviors and have immense potential as biomarkers for PDAC diagnosis and prognostication. This review provides an overview of EV proteins regarding PDAC diagnosis and prognostic implications as well as disease progression.

The role of inflammation in cancer is a topic that has been investigated for many years. As established, inflammation emerges as a defining characteristic of cancer, presenting itself as a compelling target for therapeutic interventions in the realm of oncology. Controlling the tumor microenvironment (TME) has gained paramount significance, modifying not only the effectiveness of immunotherapy but also modulating the outcomes and prognoses of standard chemotherapy and other anticancer treatments. Immunotherapy has surfaced as a central focus within the domain of tumor treatments, using immune checkpoint inhibitors as cancer therapy. Immune checkpoints and their influence on the tumor microenvironment dynamic are presently under investigation, aiming to ascertain their viability as therapeutic interventions across several cancer types. Cancer presents a significant challenge in humans and cats, where female breast cancer ranks as the most prevalent malignancy and feline mammary carcinoma stands as the third most frequent. This review seeks to summarize the data about the immune checkpoints cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), programmed cell death protein-1 (PD-1), V-domain Ig suppressor of T cell activation (VISTA), and T-cell immunoglobulin and mucin domain 3 (TIM-3) respective ongoing investigations as prospective targets for therapy for human breast cancer, while also outlining findings from studies reported on feline mammary carcinoma (FMC), strengthening the rationale for employing FMC as a representative model in the exploration of human breast cancer.

FBXW7 is one of the most well-characterized F-box proteins, serving as substrate receptor subunit of SKP1-CUL1-F-box (SCF) E3 ligase complexes. SCF^FBXW7 is responsible for the degradation of various oncogenic proteins such as cyclin E, c-MYC, c-JUN, NOTCH, and MCL1. Therefore, FBXW7 functions largely as a major tumor suppressor. In keeping with this notion, FBXW7 gene mutations or downregulations have been found and reported in many types of malignant tumors, such as endometrial, colorectal, lung, and breast cancers, which facilitate the proliferation, invasion, migration, and drug resistance of cancer cells. Therefore, it is critical to review newly identified FBXW7 regulation and tumor suppressor function under physiological and pathological conditions to develop effective strategies for the treatment of FBXW7-altered cancers. Since a growing body of evidence has revealed the tumor-suppressive activity and role of FBXW7, here, we updated FBXW7 upstream and downstream signaling including FBXW7 ubiquitin substrates, the multi-level FBXW7 regulatory mechanisms, and dysregulation of FBXW7 in cancer, and discussed promising cancer therapies targeting FBXW7 regulators and downstream effectors, to provide a comprehensive picture of FBXW7 and facilitate the study in this field.

Over the past two decades, research into the genetic susceptibility behind pheochromocytoma and paraganglioma (PPGL) has surged, ranking them among the most heritable tumors. Massive sequencing combined with careful patient selection has so far identified more than twenty susceptibility genes, leading to an over-detection of variants of unknown significance (VUS) that require precise molecular markers to determine their pathogenic role. Moreover, some PPGL patients remain undiagnosed, possibly due to mutations in regulatory regions of already known genes or mutations in undiscovered genes. Accurate classification of VUS and identification of new genes require well-defined clinical and molecular markers that allow effective genetic diagnosis of most PPGLs.

The immune microenvironment plays a critical regulatory role in the pathogenesis of Helicobacter pylori (H. pylori). Understanding the mechanisms that drive the transition from chronic inflammation to cancer may provide new insights for early detection of gastric cancer. Although chronic inflammation is frequent in precancerous gastric conditions, the monitoring function of the inflammatory microenvironment in the progression from H. pylori-induced chronic inflammation to gastric cancer remains unclear. This literature review summarizes significant findings on how H. pylori triggers inflammatory responses and facilitates cancer development through the immune microenvironment. Furthermore, the implications for future research and clinical applications are also addressed. The review is divided into four main sections: inflammatory response and immune evasion mechanisms induced by H. pylori, immune dysregulation associated with gastric cancer, therapeutic implications, and future perspectives on H. pylori-induced gastric carcinogenesis with a focus on the immune microenvironment.