Cell cycle protein E2 (CCNE2) is a member of the Cyclin family, known for driving tumor cell proliferation and invasion. However, the mechanism of its action in head and neck squamous cell carcinoma (HNSCC) remains unclear. The aim of this study is to investigate the relationship between CCNE2 and cisplatin resistance and survival prognosis of head and neck squamous cell carcinoma. We performed transcriptomic sequencing of HNSCC and HNSCC/DDP. Kaplan-Meier analysis and COX regression analysis were used to evaluate the relationship between CCNE2 expression and survival prognosis of HNSCC patients. Multiple potential biological functions of CCNE2 in HNSCC were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Single-sample gene set enrichment analysis (ssGSEA) was used to explore tumor immune infiltration. The potential mechanism of CCNE2 was explored by molecular docking and immunoprecipitation. Cell migration, cell invasion and cell proliferation assays were used to investigate the mechanism of CCNE2 in HNSCC. CCNE2 is up-regulated in HNSCC tissues and cell lines and is associated with poor prognosis. The high expression of CCNE2 in HNSCC is associated with clinical significance. GO and KEGG analysis showed that ccne2 related genes may be involved in the regulation of DNA double-strand break repair and DNA metabolic process. CCNE2 expression was positively correlated with the infiltration levels of helper T cells, Tcm cells and Th2 cells, and negatively correlated with the infiltration levels of DC, neutrophils and pDC. CCNE2 regulates the invasion, migration and proliferation of HNSCC cells by targeting MNAT1. CCNE2 also altered cisplatin resistance in HNSCC/DDP. CCNE2 may be an independent prognostic biomarker of HNSCC through MNAT1, which provides new ideas for cisplatin resistance and therapeutic targets of HNSCC.

Angiogenesis, as a core marker of cancer survival and growth, is integral to the processes of tumour growth, invasion and metastasis. In recent years, targeted angiogenesis treatment strategies have gradually become an important direction in cancer treatment. Single-cell sequencing technology can provide new insights into targeted angiogenesis by providing a deeper understanding of the heterogeneity of tumour endothelial cells and exploring the interactions between endothelial cells and surrounding cells in the tumour microenvironment. Here, we systematically review the research progress in endothelial cell pathophysiology and its endothelial‒mesenchymal transition and illustrate the heterogeneity of endothelial cells from a single-cell perspective. Finally, we examine the contributions of different cell types within the tumour microenvironment in relation to tumour angiogenesis, as well as the latest progress and strategies in targeted angiogenesis therapy, hoping to provide useful insights into the clinical application of antiangiogenic treatment. Furthermore, a summary of the present progress in the development of potential angiogenesis inhibitors and the ongoing clinical trials for combination therapies is provided. KEY POINTS: Angiogenesis plays a key role in tumour progression, invasion and metastasis, so strategies targeting angiogenesis are gradually becoming an important direction in cancer therapy. Interactions between endothelial cells and stromal cells and immune cells in the tumour microenvironment are significant in angiogenesis. The application of antiangiogenic immunotherapy and nanotechnology in antiangiogenic therapy provides a vital strategy for prolonging the survival of cancer patients.

Neurological immune-related adverse events can manifest as paraneoplastic neurological syndrome (PNS), especially in patients with small-cell lung cancer (SCLC). We herein report a 73-year-old man with SCLC treated with an immune checkpoint inhibitor (ICI) combined with chemotherapy. Although the chemo-immunotherapy induced a favorable response to SCLC, he later developed acute cerebellar ataxia. He was diagnosed with paraneoplastic cerebellar degeneration associated with anti-Sry-like high mobility group box 1 (SOX1) autoantibody. The antibody was also identified in serum collected at the diagnosis of SCLC and before ICI administration, which retrospectively suggested that the patient was at risk of ICI-induced PNS. J. Med. Invest. 72 : 172-176, February, 2025.

An Adverse Outcome Pathway (AOP) is a conceptual framework in toxicology and risk assessment that outlines the series of events from a chemical's molecular interaction to the resulting adverse health effect. This framework offers a structured approach to organizing biological knowledge, making it especially useful for understanding the mechanisms through which chemicals cause harm. Following a comprehensive analysis of the literature, an AOP was elucidated for key events linking DNA adduct formation, caused by compounds such as platinum anticancer drugs, to tubular necrosis, resulting in kidney failure. Currently, cisplatin, carboplatin and oxaliplatin are the three most utilised Pt-based drugs used globally for the treatment of cancer. The hydrolysis of platinum anticancer agents post-cellular uptake yields electrophilic intermediates that covalently bind to nucleophilic sites on DNA to form adducts that represent the molecular initiating event. When DNA repair mechanisms become unbalanced, the nephrotoxic response following the formation of DNA adducts leads to DNA damage and mitochondrial dysfunction. These events promote the generation and release of reaction oxygen species (ROS) to induce oxidative stress, causing cell death and inflammation. Upon detachment from the basement membrane, these compromised cells are subsequently deposited in the tubular lumen. Tubular obstruction and inflammatory responses to proximal tubule insult can lead to secondary toxicity and tubular necrosis, further exacerbating kidney injury and precipitating a progressive decline of renal function, finally resulting in kidney failure.

Exercise is an important tool which has been shown to help patients manage many of the side effects of their cancer treatment, reduce toxicities, and improve prognosis. The benefits of exercise have been well documented, however, performing regular exercise during treatment remains a challenge for most patients. The Flexible Individualised ExeRcise programme for cancer patients during ChEmotherapy (FIERCE) is an exercise programme that has been co-designed by healthcare professionals and people with a personal lived experience of chemotherapy. The primary aim of this study is to examine the feasibility of delivering the FIERCE programme for cancer patients during chemotherapy.

Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for cancer. However, frequent and sometimes life-threatening immune-related adverse events (irAEs) are associated with ICI treatment. Therefore, it is imperative to establish a model for predicting the risk of irAEs to identify high-risk groups, enable more accurate clinical risk‒benefit analysis for ICI treatment and decrease the incidence of irAEs. However, no ideal model for predicting irAEs has been applied in clinical practice. The aim of this study was to analyze the systemic immune characteristics of patients with irAEs and establish a model for predicting the risk of irAEs.

Retinopathy of prematurity (ROP) is the leading preventable cause of childhood blindness. A timely intravitreal injection of antivascular endothelial growth factor (anti-VEGF) is required to prevent retinal detachment with consequent vision impairment and loss. However, anti-VEGF has been reported to be associated with ROP reactivation. Therefore, an accurate prediction of reactivation after treatment is urgently needed.

There is an urgent need for the development of safe and effective modalities for the treatment of diseases owing to drug resistance, undesired side effects, and poor clinical outcomes. Combining cell-targeting and efficient cell-killing properties, peptide-drug conjugates (PDCs) have demonstrated superior efficacy compared with peptides and payloads alone. However, innovative molecular designs of PDCs are essential for further improving targeting precision, protease resistance and stability, cell permeability, and overall treatment efficacy. Several strategies have been developed to address these challenges, such as multivalency approaches, bispecific targeting, and long-acting PDCs. Other novel strategies, including overcoming biological barriers, conjugating novel functional payloads, and targeting macropinocytosis, have also shown promise. This perspective compiles the most recent strategies for enhancing PDC treatment efficacy, highlights key advancements in PDC, and provides insights on future directions for the development of novel PDCs.

Current treatments for advanced prostate cancer (PCa) primarily target the androgen receptor (AR) pathway. However, the emergence of castration-resistant prostate cancer (CRPC) and resistance to AR pathway inhibitors (APPIs) remains ongoing challenges. Here, we present BSJ-5-63, a proteolysis-targeting chimera (PROTAC) targeting cyclin-dependent kinases (CDKs) CDK12, CDK7, and CDK9, offering a multipronged approach to CRPC therapy. BSJ-5-63 degrades CDK12, diminishing BRCA1 and BRCA2 expression and inducing a sustained "BRCAness" state. This sensitizes cancer cells to PARP inhibitors (PARPis) regardless of their homologous recombination repair (HRR) status. Furthermore, CDK7 and CDK9 degradation attenuates AR signaling, enhancing its therapeutic efficacy. Preclinical studies, including both in vitro and in vivo CRPC models, demonstrate that BSJ-5-63 exerts potent antitumor activity in both AR-positive and AR-negative setting. This study introduces BSJ-5-63 as a promising therapeutic agent that addresses both DNA repair and AR signaling mechanisms, with potential benefits for a board patient population.

Cancer development is a dynamic and continuously evolving process, with the emergence of drug-resistant cancer cells being one of the primary reasons for the failure of traditional treatments. Adaptive therapy, as an emerging cancer treatment strategy, is increasingly being applied in oncology. In this study, we incorporate pharmacokinetics into a cancer evolutionary game theory model and propose an optimal control problem constrained by maximum drug concentration and maximum tumor burden. Firstly, we demonstrate the existence of an optimal control for this problem. Secondly, using Pontryagin's minimum principle, we formulated the structure of the optimal control to design an optimal adaptive therapy strategy. Finally, through numerical simulations, we compare the optimal adaptive therapy strategy with other adaptive therapies and traditional treatments, and further develop personalized treatment plans for different patient groups. The results demonstrate that the optimized adaptive treatment strategy effectively preserves a high survival rate of healthy cells during treatment. By maintaining drug-sensitive and drug-resistant cell populations in a state of low-level competition, this approach prevents the proliferation of drug-resistant cells, reduces the tumor burden on patients, and extends overall survival.

New regimens have emerged as third-line or later therapies for metastatic colorectal cancer (mCRC), including regorafenib dose optimization (ReDO), trifluridine/tipiracil and bevacizumab (TAS-BEV) combination therapy, and fruquintinib. We evaluated relative cost-effectiveness of these therapies in patients with mCRC from a US payer's perspective.

Background: Among rheumatologic diseases following therapy with immune checkpoint inhibitors (ICIs), the cases of cancer patients diagnosed as having polymyalgia rheumatica (PMR), particularly with nivolumab and pembrolizumab, has been steadily rising in published reports. Objectives: We performed a systematic review of published case reports with the aim of answering these questions: (1) Is PMR following therapy with nivolumab and pembrolizumab an adverse drug reaction (ADR)? (2) Is there a difference between cases of PMR following therapy with nivolumab and those following therapy with pembrolizumab? Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search in three main bibliographic databases: MEDLINE (Ovid interface), EMBASE, and COCHRANE Library was carried out on 27 December 2024. This systematic review has no registration number. Results: Data were extracted from 12 patients. Namely, 5 cases followed treatment with nivolumab and 7 with pembrolizumab. Validated scales for ADR assessment-such as Naranjo's scale-were not used in 10 out of the 12 patients. Additionally, validated diagnostic or classification criteria for PMR were used in the majority of case reports related to nivolumab. On the contrary, clinical judgment alone was the rule in almost all case reports on pembrolizumab. Finally, the time interval between PMR manifestations and nivolumab/pembrolizumab therapy ranged from one to 14 cycles (fully compatible with pharmacokinetics). Conclusions: Our literature review highlighted significant methodological blurred lines in the categorization of PMR following therapy with nivolumab or pembrolizumab.

Advanced cervical cancer remains associated with high mortality rates. While pembrolizumab has improved clinical outcomes in cervical cancer, the therapeutic efficacy in advanced stages is often compromised by immune-related adverse events (irAEs). This study aimed to systematically analyze pembrolizumab-associated adverse events (AEs) in cervical cancer using the FDA Adverse Event Reporting System (FAERS) database, providing new insights for optimizing clinical practice.

This study conducted a network meta-analysis to evaluate and rank the safety and efficacy of programmed cell death protein-1 (PD-1) inhibitors for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC).

Cisplatin-based chemotherapy resistance is a common issue for cancer clinical efficacy. Metformin is being studied for its possible anticancer effect. The present study aimed to investigate whether metformin affects the chemosensitivity of gastric cancer to cisplatin and reveal the molecular mechanism. In this study, the effects of combination therapy with metformin and cisplatin on cell viability, cell apoptosis, malondialdehyde, superoxide dismutase, reactive oxygen species level, glucose uptake, lactate production, protein level, and xenograft tumor formation were analyzed in gastric cancer cells. Immunohistochemical staining was performed to detect Ki67 expression in matched tumor samples. The results showed that NCI-N87 and SNU-16 cells were most resistant and sensitive to cisplatin, respectively. Metformin treatment increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Furthermore, overexpression of nuclear factor erythroid 2-related factor 2 (Nrf2) reversed the effects of metformin in the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. Metformin activated p53 and AMPK pathways in cisplatin-induced NCI-N87 cells, which were reversed by upregulating Nrf2. BAY-3827 (AMPK inhibitor) or p-nitro-Pifithrin-α (p53 inhibitor) treatments also reversed the effects of metformin increased the cisplatin sensitivity of gastric cancer by inhibiting cell viability and metabolic reprogramming and promoting cell apoptosis and oxidative stress. These results suggest that metformin significantly increases chemosensitivity of gastric cancer to cisplatin by inhibiting Nrf2 expression and metabolic reprogramming and activating oxidative stress and the pathway of p53 and AMPK.

Immune-related adverse events (irAEs) are common side effects of immune checkpoint inhibitor (ICI) cancer therapy, affecting approximately half of ICI-treated patients. irAEs may be severe and result in hospitalization. This study examined the risk factors and outcomes of irAE-related hospitalization.

Patients with breast cancer receiving chemotherapy frequently experience amenorrhea due to the cytotoxic effects of drugs, resulting in ovarian suppression and impacting reproductive health. This study aimed to prospectively investigate the incidence of clinical amenorrhea defined as the cessation of menstrual bleeding for at least three consecutive months and and biochemical amenorrhea, characterized by serum estradiol levels < 20 pg/mL and FSH levels ≥ 40 mIU/mL, using clinical and biochemical methods to determine their relation and identify the predictive factors for early amenorrhea.

In the clinical management of cancers, the emergence of chemoresistance represents a profound and imperative "pain point" that requires immediate attention. Understanding the mechanisms of chemoresistance is essential for developing effective therapeutic strategies. Importantly, existing studies have demonstrated that glucose metabolic reprogramming, commonly referred to as the Warburg effect or aerobic glycolysis, is a major contributor to chemoresistance. Additionally, lactate, a byproduct of aerobic glycolysis, functions as a signaling molecule that supports lysine lactylation modification of proteins, which also plays a critical role in chemoresistance. However, it is insufficient to discuss the role of glycolysis or lactylation in chemoresistance from a single perspective. The intricate relationship between aerobic glycolysis and lactylation plays a crucial role in promoting chemoresistance. Thus, a thorough elucidation of the mechanisms underlying chemoresistance mediated by aerobic glycolysis and lactylation is essential. This review provides a comprehensive overview of these mechanisms and further outlines that glycolysis and lactylation exert synergistic effects, promoting the development of chemoresistance and creating a positive feedback loop that continues to mediate this resistance. The close link between aerobic glycolysis and lactylation suggests that the application of glycolysis-related drugs or inhibitors in cancer therapy may represent a promising anticancer strategy. Furthermore, the targeted application of lactylation, either alone or in combination with other treatments, may offer new therapeutic avenues for overcoming chemoresistance.

Pazopanib is approved for metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma (STS) in a dose of 800 mg once daily (QD) taken under fasted conditions. In clinical practice, approximately 60% of patients require dose reductions due to toxicity, with severe liver toxicity necessitating treatment interruptions in over 10% of cases. While a trough concentration (Cmin,ss) target of ≥ 20.5 mg/L has been established for mRCC efficacy, no specific threshold exists for liver toxicity. The objectives of this study were to develop a population pharmacokinetic (POPPK), an exposure-liver toxicity, and an exposure-tumor size dynamics model to optimize pazopanib initial dose in real-world patients.

This study aims to evaluate the ultrasound-assisted synthesis of silver nanoparticles (AgNPs) based on an aqueous extract of Ruta graveolens L. to reduce Ag+ to Ag0. In addition, the biological activity of the synthesized AgNPs was evaluated against tumor cells. The following parameters were evaluated for the synthesis: proportion between Ag+ solution (0.1 mol L-1 Ag+) and R. graveolens L. extract, pH of R. graveolens L. extract (5, 7, and 9), temperature of solution containing Ag+ and R. graveolens L. extract, ultrasound (US) type (bath and probes), and the parameters for US as frequency (37, and 80 kHz for bath and 20 kHz for probes), amplitude and time of application of US. In order to confirm the US effect, "silent" experiments (without US) were performed. Using the optimized conditions (US bath, proportion between Ag+ solution and R. graveolens L. of 1 + 5, v v-1, 80 kHz, 70 % amplitude, 70 °C, pH 9, and 25 min of sonication time) it was possible to obtain mean size, PI, and zeta potential of AgNPs of 30 nm, 0.129, -34.44 mV, respectively. For comparison of results, AgNPs synthesized in the "silent" condition presented mean size, PI, and zeta potential of 66 nm, 0.412, and -22.12 mV, respectively. The US synthesized AgNPs were lower, more uniform, and stable when compared with magnetic stirring. In addition, the morphology of AgNPs using US was predominantly spherical and monodisperse. The biological activity using cell lines HaCat (keratinocytes), L929 (fibroblasts), and B16-F10 (melanoma) against nanoparticles synthesized using US was evaluated against the different cell lines and the antioxidant activity of the AgNPs was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A higher cytotoxic effect on the melanoma cell line (IC50 = 2.12 µg mL-1) compared to normal cells. A good result was found in the DPPH assay, with an IC50 of 234.3 µg mL-1 for free radical scavenging. Therefore, the US technology presents a promising and sustainable green method avoiding the use of toxic reagents and obtained AgNPs showed potent anticancer activity.