Neutrophils are the first line of defense in nonspecific immunity (innate immunity) and interact with other immune cells to participate in specific defense mechanisms (adaptive immunity). Studies have shown that the tumor microenvironment (TME) mediates tumor development and recruits neutrophils into tumors to become tumor-associated neutrophils (TANs), an important part of TME, and achieve extended lifespan. TANs can be differentiated into the antitumor or protumor phenotype, and play an important role in tumor occurrence, proliferation and recurrence, invasion and metastasis, angiogenesis, cell necrosis, and so on. Here, we summarize the TAN origin and subtypes found through Single-cell RNA sequencing analysis in different types of tumors in recent literature, and the molecular mechanisms underlying their antitumor and protumor effects on tumors. We focus on the interaction between TANs and immunosuppressive or immunostimulatory TME, as well as signal pathways such as transforming growth factor β (TGF-β) associated with TAN phenotype transition. Based on the summarized mechanisms, we focus on the potential application and latest strategies of TAN-based immunotherapy, chemotherapy, and combination therapy in the preclinical study and clinical trials of tumors. The discussion on promising therapy encompasses five key areas: inhibition of the tumor-promoting effect of TANs, enhancement of the antitumor effect of TANs, targeting the interaction between TANs and the TME, reprogramming of TANs, and drug delivery carriers. Finally, we discuss the potential of TANs and their related markers as emerging biomarkers for predicting the prognosis of cancer patients.

Gastric cancer is one of the most common malignant tumors in the digestive tract, which has the characteristics of high morbidity and mortality. However, gastric cancer is not achieved overnight but is gradually developing through the interaction of many factors. Therefore, actively delaying or blocking the "inflammation-cancer" transformation in gastric mucosa is the key to treatment. Nod-like receptor protein 3(NLRP3) inflammasome is a multi-protein signal complex and one of the important innate immune signal receptors. Inflammation plays an important role in the occurrence and development of gastric cancer, and continuous inflammation mediation will trigger the transformation from inflammation to cancer. Therefore, the significance of NLRP3 inflammasome to gastric mucosa lies in the transformation between inflammation and cancer. Traditional Chinese medicine(TCM) has the functions of multi-components, multi-targets, and few adverse reactions. A large number of studies show that TCM and related monomers have significant effects in treating liver, kidney, and immune diseases through mediating NLRP3 inflammasome, but there is less research on the "inflammation-cancer" transformation in gastric mucosa. By combing the NLRP3-related nuclear factor-κB transcription factor(NF-κB), hypoxia inducible factor-1α(HIF-1α), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), and other signal pathways, this paper clarified their mechanisms in the "inflammation-cancer" transformation in gastric mucosa, delayed the process of "inflammation-cancer" transformation in gastric mucosa through four aspects: energy metabolism, pyroptosis, immune response, and vascular endothelial growth factor, and prevented and treated "inflammation-cancer" transformation in gastric mucosa from three aspects: TCM monomer, TCM compound prescription, and other therapies, so as to provide ideas for the subsequent treatment of "inflammation-cancer" transformation in gastric mucosa with TCM.

Bronchopulmonary carcinoids are rare neuroendocrine tumors, categorized as either typical (low-grade malignancy) or atypical (intermediate-grade malignancy), with an incidence of approximately 0.5 per 100000 people. One third of patients remain asymptomatic, while others may present with symptoms such as cough, hemoptysis, and recurrent infections, often resulting from bronchial obstruction. Endocrine syndromes, like carcinoid- or Cushing syndrome, are rare in pulmonary carcinoids.The prognosis of these tumors largely depends on histological classification and disease stage at diagnosis. Typical carcinoids, which are less aggressive, show higher 5- and 10-year survival rates compared to atypical carcinoids. Diagnostic factors such as tumor size, chromogranin A (CgA) levels, and clear differentiation from other lung pathologies, including carcinomas and metastases, are essential for accurate diagnosis and therapy planning.Due to the rarity of carcinoids, treatment requires an interdisciplinary approach. Surgical resection remains the preferred therapy for localized carcinoids, offering the potential for prolonged survival. Early detection and complete tumor removal are crucial to optimizing outcomes and minimizing the risk of recurrence.

Lung cancer has the second highest occurrence and lowest survival rate among all cancers and incidence rates are increasing. From the tumor milieu, tumors exude chemokines and cytokines that hassle the pulmonary drug administration hinders the success of treatment. A few mutations lead to generation of lungs cancer. It has prominent levels of mutated genes such as TP53, KRAS, MET, and EGFR. Various molecular pathways involved in causing lung cancer such as PTEN/PI3K/AKT pathway, JAK/STAT pathways, RAF-MEK-ERK, PI3K-AKT-mTOR, and RALGDS-RA, PI3K, AKT, and PI3K/AKT/mTOR pathway. Inhibition of such biological pathway through active targeting, using various biological inhibitors, and blockers could help in treating and recurrence of lungs tumor. The conventional therapeutic modalities concomitant with personalized genomic nanomedicine can have potential in improving treatment regimen. This study explored the different genomic changes that occur due to the prime etiological factors, their reported treatment profile, and nanocarrier mediated therapeutic strategy by targeting tumor microenvironment (TME). Nanocarriers confront multiple obstacles in their journey to the TME therapeutic approach as leaky vasculature, large fenestration, and usually carried off from immune system and phagocytosis process. However, formulators designed a bio-functionalized carrier that enable to evade opsonization, escape immune system, modulate TME, identify reticuloendothelial system, and thus facilitates biological interaction, and enhance cellular uptake.

Triple-negative breast cancer (TNBC) was first described as a distinct disease entity 20 years ago. Since that time, there has been tremendous effort invested in understanding the clinical features and biology of this breast cancer subtype and developing novel therapeutics specifically targeted for this group of tumors. This review will focus on therapeutic advances in the treatment of metastatic TNBC, outlining successes that contributed to expanded treatment options for advanced TNBC at present and highlight areas of ongoing investigation with potential to further advance treatment paradigms for this aggressive breast cancer subtype. Since 2018, five new therapies have been introduced into clinical practice for the treatment of advanced TNBC. Poly(ADP-ribose) polymerase inhibitors represent the only success for genomically targeted therapy, and this is an option only for a small subgroup of patients with TNBC and a germline BRCA1 or BRCA2 pathogenic variant. Pembrolizumab is currently the only PD-1 checkpoint inhibitor approved in the United States in combination with chemotherapy in the first-line setting and is an option for roughly 40% of patients with PD-L1 positive tumors. Antibody-drug conjugates have been an important advance in the treatment of advanced TNBC, although these drugs do not represent a TNBC-specific advance as both sacituzumab govitecan and trastuzumab deruxtecan have activity in breast tumors beyond TNBC. Thus, despite significant strides over the past decade, significant unmet clinical need persists, and novel therapeutics remain a pressing need for the treatment of advanced TNBC.

Traditional surgical approaches to all oropharyngeal cancer included open surgery via mandibulotomy or mandibular swing procedures-extensive surgery that often led to tracheostomy, gastrostomy tube dependence, and prolonged hospital stay. As HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) began to increase in prevalence, it became clear that this new disease entity was associated with improved survival. There was therefore a strong desire from surgeons and oncologists to reduce the morbidity associated with its management. The paradigm shift to transoral robotic surgery and transoral laser microsurgery for selected patients with HPV oropharynx cancer has allowed for avoidance of tracheostomy, mandibulotomy, and feeding tube while preserving speech and swallow function. Current research focuses on de-escalating adjuvant treatment in appropriate cases to reduce morbidity without impacting oncologic outcome.

Standard of care for locoregionally advanced HPV-positive OPSCC is definitive chemoradiation with doses up to 70 Gy and concurrent cisplatin. Radiation techniques have evolved considerably from 3D conformal radiotherapy (3D CRT) to the now widely used intensity-modulated radiotherapy (IMRT) and volumetric modulated arc radiotherapy (VMAT). Many centers are also incorporating stereotactic body radiation therapy (SBRT) and proton therapy to deliver even more conformal treatments that can minimize dose to normal organs at risk, thereby improving the therapeutic ratio. We review here the advancements and current landscape of radiation therapy for HPV+ OPSCC.

This review assesses the efficacy and safety of EBRT + VBT versus VBT alone in intermediate- to high-risk endometrial cancer.

Prostate-specific antigen (PSA) has served as a screening tool for prostate cancer (PCa) for over 30 years, but its low specificity remains a significant limitation. Liquid biopsy based on promoter methylation, an epigenetic modification, holds significant potential to complement PSA testing and enhance the diagnostic accuracy of PCa. Our objective was to assess the diagnostic accuracy of liquid biopsy for promoter methylation in PCa.

Multiple myeloma (MM) is a malignancy of clonal plasma cells that arises from precursor conditions, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Disease progression is driven by a complex interplay of genetic alterations, epigenetic dysregulation, and support from the bone marrow microenvironment. Early events such as chromosomal translocations (e.g. t(4;14)), copy number abnormalities (e.g. del(17p), gain(1q)), and driver mutations in KRAS, NRAS, TP53, and DIS3 promote clonal evolution. These are complemented by non-coding regulatory mutations, aberrant splicing, and dysregulated non-coding RNAs that contribute to transcriptional reprogramming. The tumor microenvironment further supports MM progression through cytokine signaling, immune evasion, and enhanced angiogenesis. MM cells also undergo metabolic rewiring, favoring glycolysis, oxidative phosphorylation, and amino acid metabolism to sustain growth and resist therapy. Epigenetic alterations-including DNA methylation changes, histone modifications, and chromatin remodeling-shape gene expression and reinforce malignant behavior. This review comprehensively examines the genetic, epigenetic, and molecular alterations that underlie the initiation and progression of MM and its precursor states, with particular emphasis on the interplay between plasma cell-intrinsic mechanisms and microenvironmental influences. These insights help elucidate the biological complexity of MM pathogenesis and inform future research directions.

Surgery is considered a necessary treatment for gastric cancer (GC), but the extent of resection remains controversial. This study aimed to evaluate the efficacy of non-complete omentectomy (NCO) in GC patients undergoing radical gastrectomy.

Recurrent anal cancer (AC) often requires surgical intervention, especially when large perineal defects must be reconstructed. These cases are complicated by poor tissue vascularity and comorbid conditions such as peripheral arterial disease (PAD).

TP53-mutated acute myeloid leukemia (AML) remains one of the most treatment-resistant hematologic malignancies, with poor overall survival despite advancements in therapeutic strategies. The loss of functional p53 compromises DNA repair, apoptosis, and genomic stability, rendering both conventional and novel therapies largely ineffective. This review evaluates the efficacy of various treatment approaches, including intensive chemotherapy (IC), hypomethylating agents (HMAs), venetoclax-based regimens, and immune checkpoint inhibitors. Additionally, we discuss emerging strategies such as p53 reactivation, multi-targeted inhibition, and novel immunotherapies, including bispecific T-cell engagers (BiTEs) and CAR-T cell therapy. Current treatment options provide limited benefits in TP53-mutated AML, with complete remission rates ranging from 13% to 46% and median overall survival of only 6.1-6.5 months. Allogeneic stem cell transplantation (allo-SCT) offers minimal survival advantage due to high relapse rates. Despite promising preclinical data, checkpoint inhibitors and TIM-3 blockade have failed to demonstrate significant clinical efficacy, likely due to the immunosuppressive tumor microenvironment. Novel approaches, such as APR-246 (eprenetapopt) and MCL-1/CHK1 inhibitors, are under investigation, but their therapeutic impact remains uncertain. The failure of single-agent therapies underscores the need for combination strategies targeting multiple resistance mechanisms. Future research should focus on integrating targeted inhibitors with immunotherapy and bone marrow microenvironment modifiers. While TP53-mutated AML remains a formidable challenge, ongoing advances in precision medicine and immunotherapy hold the potential to improve patient outcomes.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the malignancies with the highest mortality rates, and outcomes are particularly poor in cases of liver metastasis. Early or recurrent metastatic PDAC significantly worsens patient outcomes and presents substantial clinical challenges. Checkpoint-based immunotherapy has largely been ineffective for most pancreatic cancer patients. This ineffectiveness is not well understood, as clinical trials often involve patients with advanced diseases, such as liver and peritoneal metastases, while most preclinical studies focus on primary tumors. Recent findings indicate that the immunosuppressive tumor microenvironment (TME) is a major obstacle to effective immunotherapy in PDAC, with the metastatic immune microenvironment differing significantly from that of primary tumors. This review explores the distinct immunosuppressive mechanisms at various stages of PDAC progression, including primary tumors, pre-metastatic niches, and metastatic sites. Myeloid cells, such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), play pivotal roles in shaping the TME and suppressing anti-tumor immunity. Particular focus is placed on current clinical immunotherapy strategies targeting myeloid cells, and combinations with conventional chemoradiotherapy, considering contemporary knowledge and future trends. Advancements in single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics have provided deeper insights into the molecular intricacies and diversity of PDAC, revealing potential therapeutic targets. Innovative strategies targeting myeloid cells, including CD40 agonists and CSF-1R inhibitors, are being explored to reprogram the TME and enhance the efficacy of immunotherapies.

Cervical cancer is a common malignant tumor in women, and human papillomavirus (HPV) infection is a major cause of cervical cancer. Tumor-infiltrating lymphocytes (TILs) are a heterogeneous group of lymphocytes primarily composed of T lymphocytes found within the tumor parenchyma and stroma. These cells can be isolated from tumor tissue, activated, expanded in vitro, and reinfused into the patient to exert an anti-tumor immune effect. As a form of personalized immunotherapy, TILs therapy has shown satisfactory efficacy and safety in advanced recurrent and metastatic cervical cancer, offering new hope to patients with advanced cervical cancer. However, TILs therapy for advanced cervical cancer still faces several limitations and challenges. This article reviews the process and latest developments in TILs therapy for advanced cervical cancer and discusses the challenges in the usage and prospects for this treatment.

Atypical placental site nodules (APSN) are a rare form of trophoblastic disease in pregnancy. There is limited research on APSN, and treatment methods are controversial, with unclear prognosis. This study collected clinical and prognostic data of 5 patients diagnosed with APSN at Xiangya Hospital of Central South University from June 2008 to June 2023, aiming to provide a better understanding of the prognosis of APSN patients and offer scientific evidence for clinical treatment. The average age of the 5 APSN patients was 32.60 years, and all patients underwent dilation and curettage or hysteroscopic surgery or hysteroscopic surgery without hysterectomy. Except for one patient who was lost to follow-up after 30 days, the remaining 4 patients were followed up for 1.36 to 4.61 years. During the follow-up, gynecological ultrasound did not show abnormalities, and serum human chorionic gonadotropin (HCG) tests were negative, with no evidence of malignancy. A search of both English and Chinese databases yielded 8 articles reporting the diagnosis, treatment, and follow-up outcomes of APSN, with 37 cases cumulatively followed up. Among them, 2 (5.41%) cases developed epithelial trophoblastic tumors or placental site trophoblastic tumors during follow-up, but there is insufficient evidence to determine whether these tumors directly originated from APSN or were secondary to APSN. Currently, there is no direct evidence suggesting that APSN has the potential for malignant transformation. Patients with APSN who have completed their childbearing may consider preserving their uterus, but close follow-up is needed to further evaluate the prognosis.

Recapitulating in vivo conditions of metabolism remains a challenging subject in biomedical research such as ADME-Tox assays (absorption, distribution, metabolism, excretion, and toxicity). The advanced technologies using 3D co-culture methods enabled researchers to develop cell-cell and cell-extracellular matrix (ECM) interactions similar to the natural liver, resulting in the improvement of the metabolic performance of ex vivo cultured primary hepatocytes (PHs). Although PHs are the best candidates in cell-based drug screening methods, access to these cells is limited. The application of stem cell-derived hepatocyte-like cells (HLCs) could overcome these limitations in high-throughput assessments. However, the functional capacity of HLCs is not enough. Hepatoma cells could be reliable substitutes for PHs and HLCs; however, compared to PHs, their metabolic performance is low. Mimicking the complexity of the liver microenvironment using hepatoma cells and liver-specific stromal cells in a 3D culture condition represents an innovative, accessible, and scalable platform to accelerate drug development if the metabolic capacity of hepatoma cells is enhanced. This can reduce time, costs, and address the ethical concerns related to animal models and pluripotent stem cells. In this manuscript, we showed that mimicking the complexity of the liver microenvironment in a 3D co-culture condition with non-parenchymal cells and improving the metabolic performance of hepatoma cells represents an innovative and accessible platform to accelerate drug discovery and development.

Head and neck squamous cell carcinoma is the seventh most common type of cancer in the world. Metastases occur in up to 40% of cases, and bones are the second most frequent site. Metastases in extremities are uncommon, with very few publications covering distal lower-limb bone metastasis.

Non-coding RNAs (ncRNAs) are crucial molecules that do not encode proteins but play roles in regulating various biological processes. Recent research highlights that ncRNAs not only control gene expression within cells but also facilitate intercellular communication via exosomes and other carriers. This function is vital in the tumor microenvironment (TME). Our review covers the structure and functions of different ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). We examine how these ncRNAs influence tumor initiation and progression. Additionally, we explore their role in promoting tumor growth or immune evasion by modulating the TME. The potential of using these ncRNAs as therapeutic targets or biomarkers for clinical use is also discussed. As our understanding of ncRNAs grows, the development of new therapies based on ncRNAs is anticipated to offer improved treatment options for cancer patients.

Cancer treatment has been revolutionized by immunotherapy and nanomedicine, offering innovative strategies to overcome the tumor microenvironment (TME) complexities. However, challenges such as therapeutic resistance, off-target effects, and immune suppression necessitate advanced delivery systems and combination approaches. Recent advancements in nanoparticle-based therapies, biomimetic platforms, and personalized immunotherapy provide promising solutions to enhance therapeutic efficacy while minimizing systemic toxicity. This review explores recent nanoparticle-mediated immunotherapy developments, highlighting strategies to optimize drug delivery, remodel the TME, and improve patient-specific treatment outcomes. A comprehensive review of recent literature focused on nanoparticle-based drug delivery, stimuli-responsive systems, biomimetic nanoplatforms, and personalized immunotherapy approaches. The effectiveness of combination therapies integrating physical and immunological strategies was also analyzed. Nanoparticle-mediated immunotherapy enables precise targeting and controlled drug release, significantly improving therapeutic outcomes. Biomimetic nanoplatforms enhance immune modulation and drug bioavailability, while personalized immunotherapy, guided by predictive biomarkers, tailors treatment to individual patients. Advanced nanomedicine strategies, including TME remodeling, targeted genome editing, and combination immunotherapies, offer promising avenues for overcoming limitations in conventional cancer treatments. Future research should optimize nanoformulations, integrate multi-modal treatment strategies, and refine biomarker-driven personalization to enhance clinical outcomes.