As the therapeutic landscape in haematological malignancies has evolved from traditional chemotherapies to novel biological, targeted, and cellular therapies, adverse event profiles have accordingly shifted with emerging and newly described chronic, cumulative, and delayed symptomatic adverse events. The current standard of toxicity reporting in clinical trials, centred on maximum-grade adverse events, is wholly inadequate for characterising the tolerability of therapies in the modern era. As such, the science of adverse event measurement, analysis, and reporting in clinical trials needs to evolve with our ever-growing repertoire of therapeutics to facilitate more comprehensive and accurate toxicity assessment for treatment decision making. In this first paper in the Adverse Event Reporting Series, a follow-up of a 2018 Lancet Haematology Commission, we review advances in the reporting of newly described adverse events and toxicity domains in haematological malignancies, emerging clinical trial designs to more accurately identify optimal dosing strategies through enhanced adverse event measurement, and novel analytic and visualisation tools to facilitate interpretation of trial adverse event data.

Taxanes that are known for their high antitumor activity, have lipophilic structures and extremely low solubility in water, which causes several challenges in the development of their formulations and clinical applications. One of the commonly accepted methods to overcome this limitation is the use of nanocrystal (NC) technology. NCs increase the solubility and bioavailability of poorly water-soluble drugs, such as taxanes, by reducing the particle size. Despite the advantages of NCs, their nanometric particle size causes physical instability issues that can compromise the efficacy and safety of the formulation. This article provides a comprehensive review of the recent advances in taxane formulations based on NCs. Common physical stability problems, such as aggregation, Ostwald ripening, sedimentation, and crystalline transformation, and common existing strategies, such as the use of electrostatic and steric stabilizers, layer-by-layer assembly technique, crosslinking and polymerization of stabilizers, and solidification of nanosuspensions, are discussed. Novel strategies including biomimetic coatings, incorporation of NCs into other nanocarriers, and surface modifications with regard to their effect on stability and drug delivery efficiency are also described. This review highlights the potential of these advanced stabilization techniques and surface modifications to improve the therapeutic efficacy and safety of NC formulations for poorly soluble taxanes, paving the way for more effective pharmaceutical applications.

Antibodies against PD-1 (PD1i), such as cemiplimab and pembrolizumab, have demonstrated significant efficacy in advanced, unresectable cutaneous squamous cell carcinoma (cSCC). These agents elicit durable responses in approximately 45% of patients, contributing to improved aesthetic, functional, and survival outcomes in a subset of individuals with advanced cSCC. This review highlights recent and ongoing research investigating the safety and efficacy of immune checkpoint inhibitors for cSCC in the curative intent perioperative settings, advanced/metastatic setting, and within the immunocompromised patient populations.

Polymeric nanoparticles are extremely valuable carriers for drug/gene delivery to treat cancer, as they can protect different therapeutic agents during blood circulation while being able to deliver them at desired locations. Owing to the versatility of polymers, it is possible to fine-tune the performance of nanocarriers by changing different properties, such as chemical structure, architecture, composition and molecular weight or even by functionalising the polymers with targeting molecules. The use of pH-sensitive polymers is a very popular strategy to prepare smart carriers, taking advantage of the acidic intratumoural environment to induce hydrophobic/hydrophilic transitions that allow fast and efficient release of small drugs or genetic material. This review summarizes the contributions of the use of promising pH-sensitive poly(2-(diisopropylamino)ethyl methacrylate) (PDPA), with pKa around 6.2, in the preparation of nanocarriers for the treatment of different types of cancer through gene therapy, drug delivery or photodynamic therapy. Interest in PDPA-based copolymers for biomedical applications is increasing, as different studies have reported successful encapsulation and delivery of different therapeutic molecules with PDPA-based smart nanocarriers. In vivo studies have shown that tumour growth can be suppressed, revealing the potential of new cancer therapies.

Tryptophan (Trp) metabolism is a complex and important biochemical process in humans. It is vital in protein synthesis and is a precursor of various bioactive molecules. Trp is metabolized through the kynurenine, serotonin and indole pathways, mediating diverse physiological functions, including neurotransmitter synthesis, immune regulation, antioxidant effects, and biosynthesis of niacin and melatonin. These metabolic pathways maintain essential functions under normal physiological conditions. However, they are significantly affected by various types of cancers. Trp metabolites regulate tumor angiogenesis, affect the self‑renewal of cancer stem cells, and participate in immune evasion and cell death through complex mechanisms. As the mechanisms underlying Trp metabolism in diseases are increasingly being elucidated, targeting Trp metabolic pathways has emerged as a promising therapeutic strategy. Further investigation of the molecular mechanisms underlying Trp metabolism and its role in diseases may provide new perspectives and approaches for diagnosing and treating diseases.

Diseases such as cancer, neurodegenerative and cardiovascular disorders, and diabetes are becoming more and more common, raising global concerns about prevention and treatment. An abnormality in cell growth can lead to the formation of tumors or neoplasms. Cancer is a global public health problem and always requires further advances in the field due to the obstacles that arise during treatment.

Quercetin, a prevalent flavonol compound, has gained attention for its multifaceted mechanisms of action against various cancers, highlighting its potential as an adjunctive therapy in cancer treatments. This review aims to systematically evaluate the structural optimization, mechanisms of action, and clinical applications of quercetin and its nano-derivatives in cancer treatment. Employing a bibliometric analysis of 6231 articles from the Web of Science Core Collection, we observed a notable increase in annual publications, particularly from the USA and China, indicating a growing interest in quercetin's therapeutic potential. Our findings reveal that quercetin enhances the efficacy of conventional therapies by modulating critical signaling pathways, thereby increasing cancer cell sensitivity while simultaneously protecting normal tissues from therapy-induced damage. Structural modifications, including glycosylation, methylation, sulfation, and glucuronidation, alongside nanoparticle formulation, significantly improve the stability, solubility, and bioavailability of quercetin, enabling targeted drug delivery. Despite the promising preclinical outcomes, the clinical translation of quercetin remains nascent, necessitating further rigorous research to validate its safety and efficacy in human subjects. In conclusion, while quercetin exhibits substantial anticancer properties and therapeutic potential, future studies should focus on expanding sample sizes, elucidating metabolic pathways, and conducting comprehensive clinical trials to inform its application in oncology.

Colloidal nanozymes, enzyme-mimetic nanocatalysts with tunable catalytic activity, are revolutionizing cancer diagnosis and therapy by integrating catalytic precision with biomedical functionality. Their ability to regulate redox homeostasis, generate reactive oxygen species (ROS), and modulate tumor microenvironments provides a foundation for targeted therapeutic interventions, while their intrinsic catalytic properties enhance biosensing and imaging for early cancer detection. However, the rational design of nanozymes remains a challenge, particularly in optimizing their catalytic efficiency, biocompatibility, and specificity for tumor-selective reactions. This review explores how surface chemistry, interfacial engineering, and catalytic mechanisms dictate nanozyme activity, stability, and interactions with biological systems. We critically analyze the fundamental catalytic mechanisms peroxidase-like, oxidase-like, catalase-like, and superoxide dismutase (SOD)-like reactions driving nanozyme applications in cancer therapy, as well as their role in biosensors, imaging probes, and theranostic platforms for early cancer diagnosis. Additionally, we examine cutting-edge surface modification strategies, including atomic dispersion, ligand coordination, and defect engineering, to enhance nanozyme selectivity and reduce off-target effects. By integrating fundamental catalysis with translational biomedical applications, this review establishes a comprehensive framework for advancing nanozyme-based diagnostics and therapeutics in precision oncology.

PARP inhibitors have profoundly changed treatment options for cancers with homologous recombination repair defects, especially those carrying BRCA1/2 mutations. However, the development of resistance to these inhibitors presents a significant clinical challenge as it limits long-term effectiveness. This review provides an overview of the current understanding of resistance mechanisms to PARP inhibitors and explores strategies to overcome these challenges. We discuss the basis of synthetic lethality induced by PARP inhibitors and detail diverse resistance mechanisms affecting PARP inhibitors, including homologous recombination restoration, reduced PARP trapping, enhanced drug efflux, and replication fork stabilization. The review then considers clinical approaches to combat resistance, focusing on combination therapies with immune checkpoint inhibitors, DNA damage response inhibitors, and epigenetic drugs. We also highlight ongoing clinical trials and potential biomarkers for predicting treatment response and resistance. The review concludes by outlining future research directions, emphasizing the need for longitudinal studies, advanced resistance monitoring technologies, and the development of novel combination strategies. By tackling PARP inhibitor resistance, this review seeks to aid in the development of more effective cancer therapies, with the potential to improve outcomes for patients with homologous recombination-deficient tumors.

To update the systematic review of assessment tools on chemotherapy-induced peripheral neuropathy (CIPN) for pediatric oncology patients based on the evidence available after the published review in 2020.

Neuroblastoma (NB) is a solid Pediatric tumor that forms in immature nerve cells. Commonly affecting the adrenal glands, spinal cord, or neck. This cancer is prevalent in children under five years old and accounts for over 15% of cancer-related deaths in this age group. Low-risk tumors can be treated surgically, intermediate-risk tumors require surgery and chemotherapy, and radiation therapy for high-risk Advancements in treatment through FDA-approved drugs and plant-derived compounds. FDA-approved drugs like Entrectinib, Dinutuximab, Unitaxin, Doxorubicin, Hydrochloride, Lorlatinib, and Crizotinib are pivotal in treating neuroblastoma. These agents inhibit pathways such as TrkA/B/C, ROS, and ALK, and the GD2 antigen. In addition to these therapies, phytochemicals have emerged as promising anticancer agents. Compounds such as quercetin, rutin, chalcone, gedunine, lycorine, withaferin A, and resveratrol have anti-cancer properties in preclinical models, targeting tumor growth and apoptosis pathways. These are improving the prevention of tumor growth through cross-reactions. Additional plant extracts have exhibited activity against neuroblastoma. This review highlights the synergistic potential of FDA-approved drugs and plant-derived phytoconstituents in improving neuroblastoma treatment outcomes.

Protein tyrosine phosphatase non-receptor 2 (PTPN2) is a well-established protein tyrosine phosphatase (PTP) that counterbalances protein tyrosine kinases (PTKs) activity by dephosphorylating tyrosine residues. Accumulating evidence demonstrates that dysregulated PTPN2 expression or activity regulates cancer biology, drives immune evasion, and confers resistance to immune checkpoint blockade therapy, establishing it as a compelling therapeutic target for cancer immunotherapy. Mechanistically, PTPN2 exerts immunosuppressive effects by dephosphorylating and negatively regulating immune response signaling, thereby dampening antitumor immunity and fostering an immunosuppressive tumor microenvironment. Recent breakthroughs in PTPN2 inhibitor development, such as small molecules, natural compounds, and PROTAC degraders, have shown promising efficacy in restoring immune-mediated tumor control. However, the anti-tumor therapy targeting PTPN2 still faces challenges, including its controversial role in some tumors, potential side effects, and the lack of highly effective and selective antagonists. In this comprehensive review, we synthesize the crucial functions of PTPN2 in tumor progression and immune regulation, systematically present the latest research progress of PTPN2 inhibitors, critically analyze unresolved hurdles in drug development, and provide strategic perspectives on addressing these challenges, with the hope of accelerating the clinical translation of PTPN2-targeted therapy from bench to bedside.

The Tricholoma (Fr.) Staude, belonging to the Tricholomataceae family, includes numerous species distributed widely across temperate regions, including Asia, Europe, and North America. The widely known species include T. matsutake (S. Ito&S. Imai) Singer, T. mongolicum Imai, and T. flavovirens Lundell, which are large, rare, and globally renowned medicinal mushrooms. In Eastern countries, Tricholoma fungi has been consumed as a vegetable for thousands of years and is also utilized in traditional Chinese medicine for its health benefits, including disease prevention and treatment. Polysaccharides, one of the key bioactive components of Tricholoma fungi, have attracted significant research interest due to their antioxidant, immunomodulatory, and antitumor activities.

Alemtuzumab is a powerful anti-CD52 drug that is an established treatment option in patients with multiple sclerosis due to its proven efficacy. However, in about 50% of patients, the use of alemtuzumab is burdened by the development of secondary autoimmune thyroid diseases, constituting a range of alemtuzumab-induced autoimmune thyroid diseases (AIATDs). Graves' disease (GD) is the most common AIATD, with an incidence of approximately 60%, and presents different characteristics from the conventional form. Indeed, GD with a fluctuating course is significantly more prevalent (15-50%), which poses a major challenge for physicians in its management. Other AIATDs also exhibit distinct features compared to their conventional counterparts; notably, hypothyroidism is frequently associated with TSH-receptor blocking antibodies, and alemtuzumab-induced GD demonstrates a higher rate of fluctuating course and potential for spontaneous remission. Alemtuzumab-induced thyroid eye disease (TED) is less common than conventional TED, with similar clinical and management characteristics. In this review, we summarize the latest evidence, also from real-world studies, with a focus on clinical management and possible predictors of AIATDs.

The aim of this study was to reveal the hepatotoxicity profile of different immune checkpoint inhibitor (ICI) used strategies in patients with Hepatocellular carcinoma (HCC) by meta-analysis.

Cancer is a multifaceted disease that occurs when cells proliferate and migrate in an uncontrolled and unregulated manner. The development of cancer is the result of the interaction of a number of factors, including genetic mutations, environmental factors and lifestyle habits. There are many pharmacological and natural compounds that can be used to prevent and/or treat cancer. Piperine, a naturally occurring compound with multiple therapeutic properties, is the primary bioactive component of black pepper (Piper nigrum L.), a member of the Piperaceae plant family. In recent years, it has attracted much interest as a potentially useful agent for the preventive and curative management of cancer. Results from studies of human cancer cell lines and advanced animal tumour models suggest that there are multiple pathways by which piperine may affect cancer development and metastasis. This review examines the molecular and cellular mechanisms through which piperine exerts its effects on cancer formation and progression, as well as its potential effects on various types of cancer.

In the era of precision medicine, a molecularly targeted therapeutical approach is still missing in the field of neuroendocrine neoplasms (NENs) other than for radioligand therapy (RLT). So far sunitinib is the only tyrosine kinase inhibitor (TKI) available in clinical practice for NENs in Western countries, limited to advanced, progressing pancreatic neuroendocrine tumors (NETs). A few TKIs worldwide reached an advanced stage of clinical investigation with promising results.

Diabetic retinopathy (DR), which affects over millions of individuals globally, is the leading cause of permanent visual loss. Current therapies, including as intravitreal anti-vascular endothelial growth factor (VEGF) medications and laser photocoagulation, are limited by frequent dosing and side effects. Liposomes, with their ability to encapsulate hydrophilic and hydrophobic medications, offer tailored delivery, prolonged release, and low systemic toxicity. This study looks at advances in liposomal formulations that address DR's multifactorial etiology, including as anti-angiogenic, anti-inflammatory, and antioxidant processes. We assess new preparation methods (e.g. supercritical CO2, microfluidics) and clinical considerations, including stability and cost-effectiveness. To address the heterogeneity of DR, future endeavors will prioritize combinatorial medications and customized therapy.

Blinatumomab has rapidly emerged as a cornerstone in the treatment of B-cell ALL (B-ALL) across age and risk groups. Initially approved for minimal residual disease (MRD)-positive adult B-ALL in 2018, its indications have since expanded after pivotal trials demonstrating significant efficacy. The BLAST and E1910 trials highlighted the benefit of blinatumomab in adults in MRD-positive and MRD-negative remission, respectively, with notable improvements in overall survival and relapse-free survival. In pediatric populations, studies such as the AALL1731 and a landmark trial in infants with KMT2A-rearranged B-ALL demonstrated striking reductions in relapse when blinatumomab was added to standard regimens. Similarly, in Philadelphia chromosome-positive B-ALL, blinatumomab-based regimens have enabled chemotherapy minimization while achieving durable remissions. Despite these advances, the rapid integration of blinatumomab into standard care poses challenges related to administration, toxicity management, and equitable access. Variability in inpatient observation durations, infusion bag sizes, home health availability, and handling of infusion-related complications underscore the need for standardized delivery models. Additionally, low-grade and long-term toxicities-such as neurotoxicity, cytokine release syndrome, and hypogammaglobulinemia-remain undercharacterized. Looking forward, research is focusing on optimizing the use of blinatumomab, including its integration into reduced-intensity or chemotherapy-free regimens, alternative dosing schedules, and subcutaneous administration. As clinical use expands, emphasis must shift toward developing equitable, patient-centered delivery strategies and understanding the full spectrum of toxicities to ensure optimal and accessible care for all patients with B-ALL.

Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival of patients with many different types of cancer since they were first approved by the United States in 2011. However, patients who are treated with ICIs can develop a variety of toxicities, known as immunotherapy-related adverse events (irAEs), that have the potential to affect essentially any organ system. Due to the growing use of ICIs in the field of oncology, it is likely that non-oncologist clinicians will increasingly encounter irAEs in both inpatient and outpatient environments. This review will provide an overview of both common and rare irAEs for the non-oncologist clinician, in addition to providing information about several guidelines developed by multiple organizations that can aid the non-oncologist clinician with the initial work-up and diagnosis of irAEs.