Blockage of PD-1 with drugs such as nivolumab (Nivo) and pembrolizumab (Pembro) has been successfully implemented in the treatment of Hodgkin lymphoma among other types of tumors. Exorbitant costs hinder access for many patients living in low- and middle-income countries (LMICs). Dose reductions on the basis of pharmacodynamic studies have been used to allow access to these drugs to patients with no further options because of economic constraints. In this study, we aimed to systematically review and assess evidence regarding the efficacy and safety of this adapted intervention.

Autophagy is a critical regulator of cellular homeostasis. The proteins involved in autophagy orchestrate the functions to strike the balance between cell survival and cell death in context-specific situations like aging, infections, inflammation and most importantly carcinogenesis. One of the major dead-locks in cancer treatment is the development of resistance to the available drugs (multi-drug resistance) as well as immune-suppressions in patients. Different studies over time have shown that autophagy is being involved in chemotherapy by working hand in hand with apoptosis or drug resistance through proliferative signals. Resistance to various drugs, such as, Cisplatin, Vincristine, Tamoxifen (TAM) occurs by epigenetic modifications, changed expression levels of microRNAs (miRNAs/miRs), and long non-coding RNAs (lncRNAs), which are regulated by the aberrant autophagy levels in lung, and breast cancers. More interestingly in the tumour microenvironment the immune suppressor cells also bring in autophagy in different pathway regulations either helping or opposing the whole carcinogenesis process. Macrophages, T cells, B cells, dendritic cells (DCs), neutrophils, and fibroblasts show involvement of autophagy in their differentiation and development in the tumor microenvironment (TME). Here, this extensive review for the first time tries to bring under a single canopy, several recent examples of autophagy-mediated immune regulations and autophagy-mediated epigenetically regulated drug resistance in different types of cancers.

Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), alone or in combination with immune checkpoint inhibitors, are part of the standard of care in treating metastatic renal cell carcinoma (mRCC). VEGFR-TKIs are associated with acute, chronic, and potentially dose-limiting toxicities requiring treatment modifications and discontinuations.

Zelenectide pevedotin (BT8009) is a novel Bicycle Toxin Conjugate targeting nectin-4, designed to overcome the limitations of already existing anti-nectin-4 antibody-drug conjugates such as enfortumab vedotin (EV). Its innovative molecular design enhances tumor penetration, minimizes systemic toxicity, and achieves therapeutic efficacy independent from internalization.

27-Hydroxycholesterol (27HC), a cholesterol metabolite, functions both as a selective oestrogen receptor (ER) modulator and a ligand for liver X receptors (LXRs). The discovery of 27HC involvement in carcinogenesis has unveiled new research avenues, yet its precise role remains controversial and context-dependent. In this review, we provide an overview of the biosynthesis and metabolism of 27HC and explore its cancer-associated signalling, with a particular focus on ER- and LXR-mediated pathways. Given the tissue-specific dual role of 27HC, we discuss its differential impact across various cancer types. Furthermore, we sort out 27HC-contributed drug resistance mechanisms from the perspectives of drug efflux, cellular proliferation, apoptosis, epithelial-mesenchymal transition (EMT), antioxidant defence, epigenetic modification, and metabolic reprogramming. Finally, we highlight the chemical inhibitors to mitigate 27HC-driven cancer progression and drug resistance. This review offers an updated role of 27HC in cancer biology, setting the stage for future research and the development of targeted therapeutics.

Pancreatic cancer is a highly aggressive gastrointestinal malignancy, often termed the "king of cancers" due to its notoriously high mortality rate. Its clinical characteristics, including late diagnosis, low surgical resectability, high recurrence rates, significant chemoresistance, and poor prognosis have collectively driven the persistent rise in incidence and mortality. Despite ongoing advancements in therapeutic strategies, the management of pancreatic cancer, particularly at advanced stages, remains challenging. Chemotherapy remains the mainstay of current treatment. However, the prevalent problem of chemotherapy resistance poses a significant obstacle to effective treatment. Metabolic reprogramming, characterized by alterations in glucose metabolism, lipid biosynthesis, and amino acid utilization, supports the high energy demands and rapid proliferation of cancer cells. Emerging evidence suggests that these metabolic changes, possibly mediated by epigenetic mechanisms, also contribute to tumorigenesis and metastasis. These findings highlight the critical role of metabolic alterations in pancreatic cancer pathogenesis. This review explores the relationship between metabolic reprogramming and chemotherapy resistance, discussing underlying mechanisms and summarizing preclinical studies and drug development targeting metabolism. The aim is to provide a comprehensive perspective on potential therapeutic strategies for pancreatic cancer.

Cancer-associated fibroblasts (CAFs) are prominent components of the lung tumor stroma and are known to foster tumor growth, invasion, and metastasis through extracellular matrix (ECM) and tumor stroma remodeling. The interactions of CAFs with cancer cells and other stromal components contribute significantly to the aggressive nature of lung cancer and pose challenges to conventional treatment approaches. Simultaneously, the ECM, which contains numerous proteins and other molecules surrounding cancer cells, serves as more than just a structural scaffold. In lung cancer, alterations in ECM composition and organization not only promote tumor cell proliferation and survival but also impact drug penetration, immune cell infiltration, and therapeutic resistance. Targeting the intricate interplay between CAFs and the dynamic ECM in lung cancer represents a crucial frontier in oncology research. This review aims to delve deeply into the pivotal roles of CAFs and the ECM in the tumorigenesis and progression of lung cancer. Then, the potential of utilizing adjuvants, phytochemicals, and nanoparticles to modulate the functions of CAFs and remodel the ECM in the lung tumor will be reviewed.

To minimise healthcare exposure in the COVID 19 era, 6-weekly extended dosing pembrolizumab became widely accepted as an alternative to 3-weekly dosing based on modelling studies. A review and meta-analysis were performed to assess the real-world safety of 6-weekly pembrolizumab in relation to 3-weekly dosing.

Currently, nanomedicines have been widely applied in the treatment of various types of tumors. However, due to the complexity of the tumor microenvironment, conventional nanomedicines often exhibit poor efficacy, insufficient site specificity, and susceptibility to off-target effects. In contrast, dual-ligand nanomedicines demonstrate superior targeting ability and drug penetration in tumor therapy. These nanomedicines are equipped with two ligands on their surface, enabling targeting of specific receptors on the same or different cells. The specific binding between ligands and receptors significantly enhances the selectivity and targeting of dual-ligand nanomedicines towards tumors. This review systematically describes the preparation of dual-ligand nanomedicines, the influencing factors, and the types of delivered drugs, focusing on the application of dual-ligand nanomedicines in targeting the treatment of various tumors. We highlight the comprehensiveness of dual-ligand nanomedicines for the treatment of tumors, including glioblastoma, lung cancer, breast cancer, gastric cancer, and many other types of tumors. Finally, the possible challenges for the future development of dual-ligand nanomedicines in terms of preparation, clinic, and safety are further analyzed. We look forward to exploring dual-ligand nanomedicines in greater depth to provide references for their future development and clinical applications.

RAC1 is a small 21 kDa RHO GTPase that plays a pivotal role in regulating actin cytoskeletal dynamics and cell growth. Alterations in the activity of RAC1 are implicated in a range of diseases, including cancer. Increased RAC1 activity, due to overexpression and/or activating mutations, drives transcriptional upregulation, reactive oxygen species production, mesenchymal-to-epithelial transition, membrane ruffling, and uncontrolled cell proliferation, which are hallmarks of an oncogenic phenotype. While RAC1-activating mutations alone do not appear sufficient to transform cells, their combination with other common mutations, such as BRAF, NRAS, or NF1, have been linked to drug resistance and significantly worsen patient prognosis and hinder treatment responses. The precise mechanisms underlying drug resistance, and the regulation of RAC1 splicing remain poorly understood. RAC1 is a challenging therapeutic target due to its ubiquitous presence and essential cellular functions. To date, there are no established standard treatments for cancers that harbour an additional RAC1 mutation or for RAC1-mediated drug resistance. Current experimental strategies aim to target RAC1 localization, its activators (e.g. guanine nucleotide exchange factors) and downstream effectors. Regulating RAC1 expression by targeting epigenetic regulators, and direct targeting of RAC1 itself, may also be possible in the near future.

Tumor heterogeneity greatly contributes to the failure of traditional cancer treatments. This leads to tumor relapse, recurrence, and ultimately metastasis, presenting serious clinical challenges. In recent decades, advances in antibody-based immunotherapy have emerged as promising new pillars to combat cancers. Although single payload antibody drug conjugates (ADCs) have resulted in drastic improvements in patient outcomes compared with unconjugated antibodies, multiple de novo and acquired resistance mechanisms inherent with cancer cells have left patients with less than desired outcomes. Newer studies are exploring the use of dual and multiple payload ADCs to enhance effectiveness. These payloads include chemotherapeutic and/or radiotherapeutic agents. The approaches leverage the synergistic effects of the different payloads alongside the immunotherapeutic properties of the antibody carriers. This review presents a comprehensive overview of dual-payload monoclonal antibody conjugates for cancer therapy and diagnosis (theranostics). Additionally, it explores the use of various imageable radiometals that are conjugated to the ADCs for imaging/diagnosis. It discusses the role of radioisotope decay schemes (such as alpha emission, beta emission, or Auger electron emission) along with factors such as linker type and chelator, as well as drug-to-antibody ratio (DAR), which are aimed at enhancing the synergistic effects between the therapeutic payloads while ensuring safety. Because none of these dual-payload ADCs have reached the clinic, this review employs a predictive method to estimate human equivalent dose (HED), maximum tolerable dose (MTD), and radiotoxicity in humans based on preclinical data. Additionally, it discusses the combinatorial behavior of two cytotoxic payloads linked to a monoclonal antibody.

Breast cancer ranks among the most common cancers globally, with significant mortality rates in advanced stages. Despite progress in treatment, therapy resistance, particularly to radiotherapy, remains a major challenge. Radiosensitization offers a promising solution to enhance radiotherapy effectiveness. This approach specifically increases tumor cells' vulnerability to IR. Recent research has explored molecular targets and strategies to improve radiosensitivity in breast cancer. Examples include inhibiting DNA repair pathways, altering the TME, targeting signaling pathways, and using immunomodulators. These strategies not only amplify destructive effects of IR but may also reduce required radiation doses, thereby minimizing normal tissue injury. This review examines promising molecular targets and combination therapies to boost radiosensitivity in breast cancer. It also highlights recent advances in immune modulation, TME remodeling, targeted molecular therapy, and metabolic pathway targeting. These advancements offer insights into the future of radiosensitization research. By systematically analyzing these strategies, the article aims to provide a comprehensive understanding of radiosensitization's current state and future potential in breast cancer treatment.

Oral mucositis (OM) is a debilitating complication commonly experienced by patients undergoing chemotherapy and/or radiotherapy for head and neck cancers. The pathogenesis of OM involves multifaceted interplay of inflammatory, immune, and cellular damage pathways triggered by cancer therapy. The pathogenesis of OM can be delineated into five overlapping phases: initiation, signaling, signal amplification, ulceration, and healing.

Nanostructured lipid carriers (NLCs) have emerged as a promising drug delivery platform in cancer therapy, offering advantages such as enhanced drug solubility, stability, and controlled release. Recent efforts have focused on utilizing NLCs for passive and active tumor targeting to improve therapeutic outcomes. This review provides a comprehensive analysis of the role of NLCs in cancer therapy, with particular emphasis on their application in passive and active targeting strategies for precision oncology. Relevant studies were selected from recent literature, focusing on NLC formulation, targeting approaches, and therapeutic applications. NLCs enhance tumor-specific drug delivery through passive targeting via the enhanced permeability and retention (EPR) effect and active targeting via ligand-mediated mechanisms. Lymphatic-targeting NLCs enable improved drug delivery to metastatic niches, while stimuli-responsive NLCs facilitate site-specific release under tumor-associated conditions (e.g., pH, enzymatic activity, redox gradients). Advances in lipid composition, surfactant systems, and conjugation strategies significantly influence drug loading (DL), biodistribution, therapeutic efficacy, and clinical translation across various malignancies. NLCs represent a versatile and adaptable platform for precision cancer therapy. Continued optimization of formulation parameters, functionalization strategies, and clinical translation pathways is essential to fully realize their potential in targeted oncology applications.

Immune checkpoint inhibitors bring hope to cancer patients but may also lead to severe immune-related adverse events (irAEs). Although irAEs during treatment are well-characterized, delayed immune-related events (DIRE) remain underreported. Here, we report a case of sintilimab-induced delayed immune-related diabetes mellitus, accompanied by ICI-related thyroid disease (ICI-TD). Cases involving both ICI-TD and ICI-related diabetes mellitus (ICI-DM) are also relatively rare. This study systematically aggregates dual endocrine irAEs to provide valuable insights for clinical practice.

Cancer immunotherapy, which leverages the immune system to target neoplastic cells, has undergone significant transformation in recent. However, immunotherapy may have negative effects on skeletal muscle function, causing muscle wasting and functional decline in cancer patients. In this study, we review the mechanisms by which immunotherapy influences skeletal muscle, focusing on immune-related myositis, inflammation, and metabolic alterations within the tumor microenvironment (TME). The key methodologies, including biomechanical assessment techniques such as electrical impedance myography and ultrasound imaging, are discussed to provide valuable insights into process that maintain muscle integrity and function in patients receiving immunotherapy. Moreover, the dual effects of immunotherapy on tumor suppression and muscle damage are described, revealing the significance of inflammatory cytokines, immune checkpoints, and metabolic disturbances within the TME. Importantly, we propose combination therapies integrating immunotherapy and nutritional interventions or anti-inflammatory interventions as potential approaches for mitigating muscle wasting. This study highlights the need for deeper investigations to optimize immunotherapy and improve its efficacy in preserving muscle health, thereby improving patient outcomes and quality of life.

Breast cancer remains the leading cause of female mortality worldwide, necessitating innovative and multifaceted approaches to address its various subtypes. Nanotechnology has attracted considerable attention due to its nanoscale dimensions, diverse carrier types, suitability for hydrophobic drug delivery, and capacity for controlled and targeted administration. Nano-sized particles have become prevalent carriers for therapeutic agents targeting breast cancer, thanks to their reproducible synthesis and adjustable properties, including size, shape, and surface characteristics. In addition, certain nanoparticles can enhance therapeutic effects synergistically. However, the immune system often detects and removes these nanoparticles, limiting their efficacy. As a promising alternative, cell membrane-based delivery systems have gained attention due to their biocompatibility and targeting specificity. These membrane-coated drug delivery systems are derived from various cell sources, including blood cells, cancer cells, and stem cells. Leveraging the unique properties of these cell membranes enables precise targeting of breast cancer tumors and associated biomarkers. Inspired by natural structures, cell membranes disguise nanoparticles in the bloodstream, enhancing their retention time in vivo and improving tumor targeting. Consequently, cell membrane-derived nanoparticles (CMDNPs) have been investigated for their potential applications in breast cancer diagnostics, photothermal therapy (PTT), and vaccine development. This review comprehensively explores the potential and limitations of cell membrane-derived drug delivery systems in clinical applications against breast cancer.

Mitochondrial reactive oxygen species (mROS) are generated as byproducts of mitochondrial oxidative phosphorylation. Changes in mROS levels are involved in tumorigenesis through their effects on cancer genome instability, sustained cancer cell survival, metabolic reprogramming, and tumor metastasis. Recent advances in nanotechnology offer a promising approach for precise regulation of mROS by either enhancing or depleting mROS generation. This review examines the association between dysregulated mROS levels and key cancer hallmarks. We also discuss the potential applications of mROS-targeted nanoparticles that artificially manipulate ROS levels in the mitochondria to achieve precise delivery of antitumor drugs.

Nanoemulsions (NEs), colloidal systems of nanoscale droplets (~100 nm), have emerged as transformative tools in oncology due to their high surface area-to-volume ratio, tunable physicochemical properties, and capacity for targeted drug delivery. While NEs find applications across diverse fields, their urgency in breast cancer therapy stems from critical limitations of conventional treatments, including systemic toxicity, poor bioavailability, and multidrug resistance. Unlike traditional chemotherapeutics, NEs enable precise tumor targeting via passive mechanisms (eg, enhanced permeability and retention effect) and active strategies (eg, ligand-functionalized surfaces), significantly reducing off-target effects. Their ability to encapsulate hydrophobic drugs, improve solubility, and sustain controlled release enhances therapeutic efficacy while overcoming resistance mechanisms prevalent in aggressive breast cancer subtypes, such as triple-negative and HER2-positive tumors. This review comprehensively analyzes NE formulation techniques (eg, ultrasonication, phase inversion temperature, bubble bursting), stability optimization through surfactant dynamics, and predictive modeling of droplet behavior. A focal point is their role in modulating tumor microenvironments, inducing apoptosis, and inhibiting angiogenesis in preclinical breast cancer models. By spotlighting NE-driven advancements in drug accumulation, reduced relapse rates, and adaptable combination therapies, this article underscores their potential to revolutionize oncology. Future research must prioritize clinical translation, scalability, and multifunctional NE designs to address unmet needs in precision breast cancer treatment.

Sulfated polysaccharides (SPS) derived from seaweeds are precious bioactive compounds of diverse biological activities. Fucoidan is a complex SPS composed of L-fucose and sulfate groups, can be extracted from brown seaweeds, as well as microbial, insect, plant glycans, and marine invertebrates. It has gained considerable attention due to its anti-inflammatory, anticancer, antiviral, antithrombotic, hypolipidemic, and immune-modulatory properties. Recent research has focused on the extraction and extensive characterization of fucoidan. Its structural complexity, influenced by species, sources, and harvesting conditions, directly influences its bioactivity, with higher sulfation and lower molecular weight enhancing its activity. Interestingly, fucoidan oligosaccharides (FOs) play a critical role in various metabolic processes and hold significant potential in disease diagnostics. This comprehensive review explores the current status of fucoidan research, covering its sources, extraction and purification techniques, structural variations and biological activities. Additionally, we highlight its potential health benefits, providing insights for researchers interested in sulfated polysaccharides.