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Protein arginine deiminase 4 (PAD4) plays an important role in cancer progression by participating in gene regulation, protein modification, and neutrophil extracellular trap (NET) formation. Many reversible and irreversible PAD4 inhibitors have been reported recently. In this review, we summarize the structure–activity relationships of newly investigated PAD4 inhibitors to bring researchers up to speed by guiding and describing new scaffolds as optimization and development leads for new effective, safe, and selective cancer treatments. In addition, some recent reports have shown evidence that PAD4 inhibitors are expected to trigger antitumor immune responses, regulate immune cells and related immune factors, enhance the effects of immune checkpoint inhibitors, and enhance their antitumor efficacy. Therefore, PAD4 inhibitors may potentially change tumor immunotherapy and provide an excellent direction for the development and clinical application of immunotherapy strategies for related diseases.

Controlling infection in bacterial-infected wounds presents a formidable challenge, especially when compounded by additional high-risk factors that hinder the healing process during clinical interventions. Currently, the efficacy of standard therapeutic approaches often falls short, largely attributed to persistent local infections and inflammatory responses that impede healing cascades. In recent years, increasing reports on the management of hard-to-heal infected wounds have highlighted the potential of reactive oxygen species (ROS)-responsive hydrogels to facilitate wound recovery. The capacity of these hydrogels could be greatly enhanced by integrating them with traditional treatments, thereby addressing the complexities of healing in refractory infected wounds. Therefore, based on a thorough review of latest literatures, this paper comprehensively outlines the molecular mechanisms associated with hard-to-heal infected wounds, the role of ROS-responsive hydrogels in promoting healing, and a combined therapeutic strategy for wound control. It is designed to offer valuable insights to inform and advance future investigative efforts in this research field.

Oncolytic viruses (OVs) are a class of viral preparations with selective replication capability in tumor cells and the ability to activate systemic anti-tumor immunity. They have emerged as an important breakthrough in cancer treatment following chemotherapy, targeted therapy, and immune checkpoint inhibitors. This article systematically reviews the developmental trajectory of OVs from the accidental discovery of wild strains to their genetic engineering-based modification and optimization, and subsequently to accelerated clinical translation. It primarily highlights key advances in viral backbone design, immune regulatory gene insertion, and combination therapy strategies. Currently, several OV-based therapeutics have been approved for clinical use worldwide for the treatment of various solid tumors, including melanoma, glioblastoma, and head and neck cancers, demonstrating their extensive potential for broader indication coverage as evidenced by ongoing clinical trials. Although OVs possess unique advantages in their ability to remodel the tumor microenvironment and elicit both local and systemic anti-tumor effects, their clinical application still faces challenges such as limited monotherapy efficacy, barriers to systemic delivery, a lack of precision biomarkers, and issues in large-scale manufacturing and quality control. Looking ahead, by drawing on cutting-edge technologies such as CRISPR-based gene editing, reverse genetics, advanced delivery systems, and multimodal combination therapy, OVs are expected to achieve greater precision and personalization in cancer treatment, thereby promoting their wider application in the management of solid tumors.

Biliary tract cancer, which includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, presents a significant clinical challenge because of its aggressive nature and limited therapeutic options. Although standard chemotherapy regimens, such as gemcitabine and cisplatin, are used, the prognosis for advanced biliary tract cancer patients remains poor due to the rapid development of resistance. Recently, advancements in immunotherapy, particularly immune checkpoint inhibitors, have shown promise. However, the response rate in patients with biliary tract cancer is still suboptimal primarily because of the highly immunosuppressive tumour microenvironment. This microenvironment includes a complex network of tumour-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, all of which contribute to immune evasion. In this review, we discuss the molecular mechanisms that drive biliary tract cancer, focusing on genetic alterations and the role of the TME in immune suppression. We also examine current combination strategies that integrate immune checkpoint inhibitors with chemotherapy and targeted therapies, which have demonstrated superior efficacy over monotherapy. Furthermore, we explore emerging therapeutic approaches, such as metabolic modulation, CAR-T-cell therapy, and mRNA vaccines, which are reshaping the treatment landscape. Finally, we highlight the need for personalized treatment strategies and the development of predictive biomarkers to guide therapy selection. Future research should focus on refining these combination therapies, optimizing patient selection, and validating biomarkers to improve clinical outcomes and survival in biliary tract cancer patients.

This chapter contains sections titled: Introduction Antidiabetic Treatments Weight Loss Drugs Treatment of Diabetic Complications Future Strategies of Antidiabetic Therapies Summary References

Magnetic hyperthermia (MH) has been introduced clinically as an alternative approach for the focal treatment of tumors. MH utilizes the heat generated by the magnetic nanoparticles (MNPs) when subjected to an alternating magnetic field (AMF). It has become an important topic in the nanomedical field due to their multitudes of advantages towards effective antitumor therapy such as high biosafety, deep tissue penetration, and targeted selective tumor killing. However, in order for MH to progress and to realize its paramount potential as an alternative choice for cancer treatment, tremendous challenges have to be overcome. Thus, the efficiency of MH therapy needs enhancement. In its recent 60-year of history, the field of MH has focused primarily on heating using MNPs for therapeutic applications. Increasing the thermal conversion efficiency of MNPs is the fundamental strategy for improving therapeutic efficacy. Recently, emerging experimental evidence indicates that MNPs-MH produces nano-scale heat effects without macroscopic temperature rise. A deep understanding of the effect of this localized induction heat for the destruction of subcellular/cellular structures further supports the efficacy of MH in improving therapeutic therapy. In this review, the currently available strategies for improving the antitumor therapeutic efficacy of MNPs-MH will be discussed. Firstly, the recent advancements in engineering MNP size, composition, shape, and surface to significantly improve their energy dissipation rates will be explored. Secondly, the latest studies depicting the effect of local induction heat for selectively disrupting cells/intracellular structures will be examined. Thirdly, strategies to enhance the therapeutics by combining MH therapy with chemotherapy, radiotherapy, immunotherapy, photothermal/photodynamic therapy (PDT), and gene therapy will be reviewed. Lastly, the prospect and significant challenges in MH-based antitumor therapy will be discussed. This review is to provide a comprehensive understanding of MH for improving antitumor therapeutic efficacy, which would be of utmost benefit towards guiding the users and for the future development of MNPs-MH towards successful application in medicine.

Background Transarterial chemoembolization (TACE) is commonly used to treat patients with unresectable hepatocellular carcinoma (HCC); however, TACE alone has demonstrated unsatisfactory survival benefits. Our previous studies suggested that TACE plus oral medication of thalidomide, carmofur and compound mylabris capsule (TCC cocktail) may be a better therapeutic option. Methods In this randomized, open-label, multicenter clinical trial, 72 treatment-naive HCC patients were randomly assigned to receive cTACE alone or cTACE plus oral TCC cocktail between July 2018 and October 2019. The primary endpoint of this trial was the 1-, 2- and 3-year overall survival (OS) rates. The second endpoints of this trial included 1-, 2- and 3-year progression-free survival (PFS) rates, objective response rates (ORR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and safety with adverse events (AEs). Results The 1-, 2- and 3-year OS rates were significantly higher in the cTACE plus TCC group than in the cTACE group (83.2% vs 54.3%, 63.1% vs 30.1%, 37.7% vs 18.1%; p  = 0.008), with a significantly longer median OS (29.0 vs 15.0 months; p  < 0.001). Regarding the 1-, 2- and 3-year PFS rates, HCC patients in the cTACE plus TCC group also demonstrated significantly higher rates (66.3% vs 34.4%, 35.8% vs 18.8%, 31.8% vs 15.6%; p  = 0.014) and had a longer median PFS (16.0 vs 8.0 months; p  < 0.001) compared with cTACE group. All treatment-related AEs were tolerated. Conclusions For patients with unresectable HCC, TACE combined with TCC cocktail was well tolerated and significantly improved clinical outcomes. Trial registration The trial was registered at https://www.chictr.org.cn/showproj.html?proj=27493 as ChiCTR1800016335 on 25th May 2018 named an open-label, multicenter, randomized, prospective clinical trial of thalidomide based triple oral regimen for low-dose maintenance therapy after TACE in advanced hepatocellular carcinoma.

Inflammation is a complex and finely tuned component of the host defense mechanism, responding sensitively to a range of physical, chemical, and biological stressors. Current research is advancing our grasp of both cellular and molecular mechanisms that initiate and regulate interactions within inflammatory pathways. Substantial evidence now indicates a profound link between inflammation, innate immunity, and cancer. Dysregulation of inflammatory pathways is known to be a pivotal factor in the induction, growth, and metastasis of tumors through multiple mechanistic pathways. Basically, the tumor microenvironment (TME), characterized by dynamic interplay between cancerous cells and surrounding inflammatory and stromal cells, plays a central role in these processes. Increasingly, controlled acute inflammation is being explored as a promising therapeutic tool in certain types of cancer. However, inflammatory cells in the TME exhibit remarkable plasticity, with shifting phenotypic and functional roles that facilitate cancer cell survival, proliferation, and migration, especially under chronic inflammatory conditions. Additionally, signaling molecules associated with the innate immune system, like chemokines, are co-opted by malignant cells to support invasion, migration, and metastasis. These findings underscore the need for deeper insights into the mechanisms connecting inflammation to cancer pathology, which could pave the way for innovative diagnostic approaches and targeted anti-inflammatory therapies to counter tumor development. The current review underlines the critical involvement of inflammation in cancer development, examining the connection between the immune system, key inflammatory mediators, biomarkers, and their associated pathways in cancer. We also discuss the impact of inflammation-targeted therapies on anticancer signaling pathways. Furthermore, we review major anti-inflammatory drugs with potential applications in oncology, assessing how inflammation is modulated in cancer management. Lastly, we outline an overview of ongoing discoveries in the field, highlighting both the challenges and the therapeutic promise of targeting inflammation in cancer therapy.

Chimeric antigen receptor-cell therapies have demonstrated remarkable success in haematological malignancies but face significant hurdles in solid tumours. The hostile tumour microenvironment, antigen heterogeneity, limited tumour infiltration, and CAR-cell exhaustion contribute to reduced efficacy. Additionally, toxicity, off-target effects, and manufacturing challenges limit widespread clinical adoption. Overcoming these barriers requires a multifaceted approach that enhances CAR-cell persistence, trafficking, and tumour-specific targeting. Recent advancements in alternative cellular therapies, such as CAR-natural killer cells, CAR-macrophages, gamma delta CAR-T cells, and CAR-natural killer T cells, provide promising avenues for improving efficacy. These strategies leverage distinct immune cell properties to enhance tumour recognition and persistence. Furthermore, combination therapies, including chemotherapy, radiotherapy, antibodies, small molecule inhibitors, cancer vaccines, oncolytic viruses, and multi-CAR cell combination therapy, offer synergistic potential by modulating the TME and improving CAR-cell functionality. This review explores the challenges of CAR-based cellular therapies in solid tumours and highlights emerging strategies to overcome therapeutic limitations. By integrating novel cellular platforms and combination approaches, we seek to provide insights into optimising CAR-cell therapies for durable responses in solid malignancies.